Mechanism of miR-200b-3p-induced FOSL2 inhibition of endometrial cancer cell proliferation and metastasis

Mechanism of miR-200b-3p-induced FOSL2 inhibition of endometrial cancer cell proliferation and metastasis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Mechanism of miR-200b-3p-induced FOSL2 inhibition of endometrial cancer cell proliferation and metastasis Lijie He#, Jing Wang, zhe han This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4866332/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 May, 2025 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Objective The purpose of this study was to investigate how miR-200b-3p inhibits the proliferation and metastasis of endometrial cancer cells by inducing the expression of FOSL2 in the AP1 transcription family. Methods Endometrial cancer cell line HEC-1-A was divided into 12 groups: NC-mimic ( transfected with negative control NC mimic ), miR-200b-3p mimic ( transfected with miR-200b-3p mimic ), NC-suppress ( transfected with negative control NC inhibit ), miR-200b-3p inhibit group ( transfected with miR-200b-3p inhibit ), si-NC ( transfected with negative control Si-NC ), Si-FOSL2 ( transfected with Si-FOSL2 ), oe-NC ( transfected with negative control oe-NC ), oe-FOSL2 group ( oe-FOSL2 ), MiR-200b-3p mimic + oe-NC group ( co-transfected with miR-200b-3p mimic and oe-NC ), miR-200b-3p mimic + oe-FOSL2 group ( co-transfected with miR-200b-3p mimic and oe-FOSL2 ), miR-200b-3p inhibit + si-NC group ( co-transfected with miR-200b-3p inhibit and si-NC ), miR-200b-3p inhibit + si-FOSL2 group ( co-transfected with miR-200b-3p inhibit and si-FOSL2 ). Real-time fluorescence quantitative PCR, Western blot, CCK-8 assay, scratch test and Transwell assay were used to detect the expression of miR-200b-3p mRNA, FOSL2 mRNA and protein, cell proliferation, migration and invasion. Results In endometrial cancer cell lines, the expression of miR-200b-3p was significantly down-regulated (P<0.05), while the expression of FOSssL2 was significantly up-regulated (P<0.05). Compared with NC-mimic group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic group was significantly decreased (P<0.05), and the expression of E-cadherin was significantly increased (P<0.05). The cell proliferation, migration rate and the number of transmembrane cells were significantly decreased (P<0.05). Compared with the miR-200b-3p mimic + oe-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic + oe-FOSL2 was significantly increased (P<0.05), the expression level of E-cadherin was significantly decreased (P<0.05), and the cell proliferation, migration rate and the number of transmembrane cells were significantly increased (P<0.05). Compared with NC-inhibit group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibit group was significantly increased (P<0.05), and the expression of E-cadherin was significantly decreased (P<0.05). The cell proliferation, migration rate and the number of transmembrane cells were significantly increased (P<0.05). Compared with the miR-200b-3p inhibit + si-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibit + si-FOSL2 was significantly decreased (P<0.05), and the expression of E-cadherin was significantly increased (P<0.05); the cell proliferation, migration rate and the number of transmembrane cells were significantly decreased (P<0.05) Conclusion The expression of miR-200b-3p in endometrial cancer cells is down-regulated, which can inhibit the proliferation, migration and invasion of endometrial cancer cells by regulating the EMT process, and its mechanism is related to its targeted negative regulation of FOSL2 expression. Biological sciences/Cancer Health sciences/Biomarkers Health sciences/Medical research miR-200b-3p FOSL2 Endometrial cancer Cell proliferation Cell metastasis EMT Figures Figure 1 Figure 2 Figure 3 Introduction Endometrial cancer (EC) is a malignant tumor that occurs in the epithelial lining of the uterus in the female reproductive system, with adenocarcinoma being the most common, and its incidence is steadily increasing worldwide.[ 1 ] Early treatment of EC results in a relatively good prognosis, but patients with advanced or recurrent EC have a poorer clinical prognosis and a significantly lower survival rate, with 5-year survival rates of 44% and 37% in patients with pelvic and extra-pelvic metastases, respectively.[ 2 , 3 ] As the only gynecologic malignancy with an increased mortality rate,[ 4 ] there is an urgent need for further exploration of the mechanisms of its development and progression. MicroRNAs (miRNAs) is a class of small non-coding RNA (ncRNA), usually composed of 19–24 nucleotides, that can directly affect or regulate intracellular signaling pathways and indirectly influence the expression of tumor-associated proteins, thereby exerting antitumor effects or carcinogenesis.[ 5 ] A variety of miRNA have been found to be closely related to endometrial cancer development and progression.[ 6 – 8 ] Among them, miR-200b can affect cancer progression by regulating the EMT process in endometrial cancer cells.[ 9 ] miR-200b-3p, which belongs to the miR-200b family, has also been found to inhibit the proliferation, invasion, and migration ability of a variety of tumors by inhibiting the expression of downstream mRNA.[ 10 ] FOSL2, a member of the activator protein-1 (AP1) transcriptional family, is widely expressed in tissues, and is able to regulate growth, development, and immune responses, which play key roles in physiological and pathological processes.[ 11 ] Some studies have found that FOSL2 can act as a downstream target protein of miRNAs to regulate epithelial mesenchymal transition (EMT), metastasis, and other mediators of malignant tumor progression.[ 12 , 13 ] Although numerous studies have confirmed that miR-200b-3p and FOSL2 play important roles in the progression of some cancers, the roles of both in the development of endometrial cancer have not been clarified. Therefore, the aim of this study is to investigate the role of miR-200b-3p through its regulation of FOSL2 and its effect on the proliferation and metastasis of endometrial cancer cells, and to reveal its underlying molecular mechanisms. Material and Methods 1.1 Cells and Primary Reagents Human endometrial cancer (HEC-1-A, RL95-2, Ishikawa) and human normal endometrial mesenchymal hEM15A are purchased from the Shanghai Cell Bank, Chinese Academy of Sciences. 0.25% trypsin, trypsin, DMEM medium, RPMI 1640 medium, and RIPA lysate are purchased from Promega, USA. TRIzol (Invitrogen, USA). miR-200b-3p inhibitor, FOSL2 inhibitor, and β-actin are purchased from Thermo Fisher Scientific, USA. N-cadherin inhibitor, Vimentin inhibitor and human E-cadherin inhibitor are purchased from CST, USA. miR-200b-3p mimic, miR-200b-3p inhibitor, si-FOSL2, oe-FOSL2 and the corresponding negative control are purchased from Ribobio, China. wild-type FOSL2 3'UTR (FOSL2-WT), mutant FOSL2 3'-UTR (FOSL2-WT) report vectors are purchased from Vigenebio, Shandong, China.The dual-luciferase reporter gene kit is purchased from Solarbio, USA. The CCK-8 reagent and the cell cycle kit are purchased from Beyotime Biotech Inc, Shanghai, China. Transwell chamber is purchased from Thermo, USA. 1.2 Cell culture and cell transfection Endometrial cancer cell lines HEC-1-A, RL95-2, Ishikawa and human normal endometrial mesenchymal stromal cell line hEM15A were cultured in DMEM medium containing 10% fetal bovine serum (FBS) at 37℃ with 5% CO2 incubator. The HEC-1-A cell line was divided into 12 groups, and 3 replicate wells were set up in each group: NC-mimic (transfected with negative control NC mimic), miR-200b-3p mimic (transfected with miR-200b-3p mimic), NC-inhibit (transfected with negative control NC inhibit), miR-200b-3p inhibit group (transfected with miR-200b-3p inhibit), si-NC (transfected with negative control Si-NC), Si-FOSL2 (transfected with Si-FOSL2), oe-NC (transfected with negative control oe-NC), oe-FOSL2 group (oe-FOSL2), miR-200b-3p mimic + oe-NC group (co-transfected with miR-200b-3p mimic and oe-NC), miR-200b-3p mimic + oe-FOSL2 group (co-transfected with miR-200b-3p mimic and oe-FOSL2), miR-200b-3p inhibit + si-NC group (co-transfected with miR-200b-3p inhibit and si-NC), miR-200b-3p inhibit + si-FOSL2 group (co-transfected with miR-200b-3p inhibit and si-FOSL2). The miR-200b-3p mimic, miR-200b-3p inhibitor, si-FOSL2, oe-FOSL2, and the corresponding negative control were individually or co-transfected into HEC-1-A cells using the Lipofectamine 2000 kit according to the instructions. 48h later, the transfection efficiency was verified by real-time fluorescence quantitative PCR and Western blot to verify the transfection efficiency. 1.3 Real-time fluorescence quantitative PCR Total RNA was extracted using TRIzol reagent, and the RNA concentration and OD260/OD280 ratio were detected using a NanoDrop ultraviolet spectrophotometer. 10 µg of RNA was taken and reverse transcribed into cDNA, and RT-qPCR was performed using SYBR Green Mix (Thermo Fisher Scientific, USA). β-actin was used as an internal reference, and the relative gene expression was calculated using the -ΔΔCT method. Three parallels were set in each group. 1.4 Western blot Total protein was extracted using RIPA protein lysate containing 100× Cocktail and 100× PMSF, and protein concentration was determined by BCA protein assay kit. Proteins were electrophoretic transfered to PVDF membranes by 10% SDS-PAGE gel. After the transfer was completed, the membrane was closed with 5% skimmed milk for 1h at room temperature and incubated with the corresponding primary antibody at 4°C overnight. The membrane was washed with TBST buffer and incubated with the corresponding secondary antibody at room temperature for 1h. ECL reagent and chemiluminescence detection kit were used for blot analysis, β-actin was used as the internal control, and Image J v1.8 was used for blot analysis. 1.5 Bioinformatics analysis Starbase( http://starbase.sysu.edu.cn/index.php ) was used to predict the potential binding site between miR-200b-3p and FOSL2 3'-UTR. 1.6 Dual luciferase test HEC-1A cells were co-transfected with Lipofectamine 2000(miR-200b-3p mimic /NC mimic), wild-type FOSL2 3'UTR (FOSL2-WT), mutant FOSL2 3'-UTR (FOSL2-MUT). After 48h of transfection, luciferase activity was measured using Dual-Lucy Assay Kit. 1.7 Cell proliferation assay CCK-8 was used to detect the proliferative activity of cells in each group. HEC-1A cells in logarithmic growth phase were prepared into a cell suspension of 5×10 4 cells/mL, and 100 µL of the cell suspension was inoculated into 96-well plates and cultured at 37℃ with 5% CO2 for 2 to 3h. Subsequently, 10µL of CCK-8 reagent was added to each well, and the culture was continued for 2h. Absorbance values at 450nm were detected, and the data were recorded and the cell proliferation curves were plotted. 1.8 Cell scratch assay Cell migration was detected using the cell scratch assay. EC cells were inoculated in 6-well plates at a density of 1×10 5 cells/well, and when the cell fusion reached more than 80%, a 200 µL tip was used to scratch vertically at the bottom of the well plates to form cell scratches. After completion of the scratch, the cells were rinsed with PBS to remove the suspended cells. Photographs were taken at 0h and 12h after scratching with a 10x field of view. The area of the scratch at each time point was analyzed using ImageJ software, and the mobility rate was calculated. 1.9 Transwell Detection Cell invasion was detected using the Transwell assay. HEC-1A cells were inoculated at a density of 1×10 5 cells/well in the upper chamber of a small chamber containing 200 µL of serum-free medium, while 500 µL of medium containing 10% fetal bovine serum was added to the lower chamber. After 24 hours of incubation at 37°C with 5% CO2, cells remaining on the upper surface of the filter were removed, and cells migrating to the lower chamber were fixed using methanol and stained with crystal violet. Subsequently, five fields of view were randomly selected under a light microscope (10x objective), and the average cell number was calculated. 1.10 Statistical analysis GraphPad Prism statistical software is applied to analyze the data and plot. Data in this study are expressed as mean ± SD. t-test, one-way ANOVA and SNK-q test were used for comparison of measurement data. P < 0.05 is considered as significant statistically difference. Results 2.1 miR-200b-3p mimic and FOSL2 expression in EC cells The expression of miR-200b-3p is significantly down-regulated (P < 0.05) in EC cell lines compared to human normal endometrial cells. The lowest expression is found in HEC-1-A, which is selected for subsequent overexpression experiments. mRNA and protein expression of FOSL2 is significantly increased (P < 0.05) in EC cell lines, as shown in Fig. 1 and Table 1 . Table 1 miR-200b-3p mRNA and protein expression in EC cell lines (n = 3, x ± s) Groups miR-200b-3p FOSL2 mRNA FOSL2 hEM15A 1.01 ± 0.02 0.49 ± 0.02 0.58 ± 0.03 HEC-1-A 0.31 ± 0.04 1.24 ± 0.04 1.26 ± 0.11 RL95-2 0.49 ± 0.04 1.18 ± 0.12 1.13 ± 0.08 Ishikawa 0.61 ± 0.02 0.67 ± 0.06 0.74 ± 0.03 F 792.900 248.940 181.759 P P < 0.001 P < 0.001 P < 0.001 2.2 FOSL2 is a downstream target gene of miR-200b-3p The existence of potential binding site of miR-200b-3p with FOSL2 3'-UTR is predicted using Starbase(Fig. 2 A).Compared with the NC-mimic group, the expression of miR-200b-3p in the miR-200b-3p mimic group was significantly increased (P < 0.001). Compared with the NC- inhibit group, and, miR-200b-3p expression in the miR-200b-3p inhibit group was significantly decreased (P < 0.001) (Table 2 ). Compared with the Si-NC group, FOSL2 mRNA and protein expression in the Si-FOSL2 group were significantly decreased (P < 0.001). Compared with the oe-NC group, the FOSL2 mRNA and protein expression in the oe-FOSL2 group were significantly increased (P < 0.001) (Fig. 2 B and Table 3 ). Compared with the NC-mimic group, FOSL2 mRNA and protein expression in the miR-200b-3p mimic group were significantly decreased (P < 0.001). Compared with the miR-200b-3p mimic + oe-NC group, FOSL2 mRNA and protein expression in the miR-200b-3p mimic + oe-FOSL2 group were significantly increased (P < 0.001). Compared with the NC-inhibit, FOSL2 mRNA and protein expression in the miR-200b-3p inhibit group were significantly increased (P < 0.001). Compared with the miR-200b-3p inhibit + si-NC group, FOSL2 mRNA and protein expression in the miR-200b-3p inhibit + si- FOSL2 group were significantly decreased(P < 0.001), (Table 4 and Fig. 2 C). As a result of dual luciferase assay, Compared with the NC-mimic group, FOSL2-WT dual luciferase activity in the miR-200b-3p mimic group was significantly reduced (P < 0.001). Compared with the NC-inhibit group, FOSL2-WT dual luciferase activity in the miR-200b-3p inhibit group was significantly higher(P < 0.001),( Table 5 ). Table 2 miR-200b-3p mRNA expression in each group of cells (n = 3, x ± s) Groups miR-200b-3p NC-mimic 1.01 ± 0.02 miR-200b-3p mimic 0.45 ± 0.02 t 34.293 P < 0.001 NC-inhibit 0.99 ± 0.02 miR-200b-3p inhibit 2.59 ± 0.08 t 33.607 P < 0.001 Table 3 Expression of FOSL2 mRNA and protein in each group of cells (n = 3, x ± s) Groups FOSL2 mRNA FOSL2 si-NC 1.02 ± 0.02 1.01 ± 0.01 si-FOSL2 0.39 ± 0.02 0.31 ± 0.02 t 38.579 54.222 P < 0.001 < 0.001 oe-NC 0.99 ± 0.02 1.02 ± 0.03 oe-FOSL2 2.54 ± 0.08 2.64 ± 0.12 t 32.557 23.105 P < 0.001 < 0.001 Table 4 Expression of FOSL2 mRNA and protein in each group of cells (n = 3, x ± s) Groups FOSL2 mRNA FOSL2 NC-mimic 1.01 ± 0.01 0.99 ± 0.01 miR-200b-3p mimic 0.45 ± 0.02 0.39 ± 0.02 t 43.377 46.476 P < 0.001 < 0.001 miR-200b-3p mimic + oe-NC 0.42 ± 0.03 0.40 ± 0.02 miR-200b-3p mimic + oe-FOSL2 0.89 ± 0.03 0.82 ± 0.02 t 19.188 20.176 P < 0.001 < 0.001 NC-inhibit 0.99 ± 0.02 1.00 ± 0.02 miR-200b-3p inhibit 2.44 ± 0.03 2.40 ± 0.02 t 69.656 85.732 P < 0.001 < 0.001 miR-200b-3p inhibit + si-NC 1.41 ± 0.03 1.38 ± 0.03 miR-200b-3p inhibit + si-FOSL2 2.11 ± 0.02 2.09 ± 0.05 t 33.627 21.090 P < 0.001 < 0.001 Table 5 Dual luciferase assay (n = 3, x ± s) Groups FOSL2-WT FOSL2-MUT NC-mimic 1.01 ± 0.09 1.00 ± 0.11 miR-200b-3p mimic 0.49 ± 0.05 0.99 ± 0.08 t 8.748 0.127 P 0.001 0.905 NC-inhibit 0.99 ± 0.12 1.01 ± 0.08 miR-200b-3p inhibit 2.15 ± 0.08 1.00 ± 0.09 t 13.931 0.144 P < 0.001 0.893 2.3 Effect of miR-200b-3p on endometrial cancer cell proliferation, migration and invasion Compared with the NC-mimic group, showed a significant decreased the cell proliferation activity, cell migration rate, and the number of membrane-penetrating cells in the miR-200b-3p mimic group were significantly decreased (P < 0.05), the mRNA and protein expression levels of the epithelial markers, N-cadherin and Vimentin were significantly decreased (P < 0.05), and the mRNA and protein expression levels of mesenchymal marker were significantly increased (P < 0.05). Compared with the miR-200b-3p mimic + oe-NC group, cell proliferation activity, cell migration rate, and number of membrane-penetrating cells in the miR-200b-3p mimic + oe-FOSL2 group were significantly increased (P < 0.05), the mRNA and protein expression levels of N-cadherin and Vimentin were significantly increased (P < 0.05), and the mRNA and protein expression levels of E -cadherin's mRNA and protein expression levels were significantly decreased (P < 0.05). Compared with the NC-inhibit group, the cell proliferation activity, cell migration rate, and number of membrane-penetrating cells in the miR-200b-3p inhibit group were significantly increased (P < 0.05), the mRNA and protein expression levels of N-cadherin and Vimentin were significantly increased (P < 0.05), and the mRNA and protein expression levels of E-cadherin were significantly decreased (P < 0.05). Compared with the miR-200b-3p inhibit + si-NC group, the cell proliferative activity, cell migration rate, and the number of membrane-penetrating cells in the miR-200b-3p inhibit + si-FOSL2 group were significantly decreased (P < 0.05), mRNA and protein expression levels of N-cadherin and Vimentin were significant decreased (P < 0.05), and the mRNA and protein expression levels of E-cadherin were significant increased (P < 0.05), (Fig. 3 , Table 6 and Table 7 ). Table 6 Proliferative activity of each group of cells detected by CCK-8 assay (n = 3, x ± s) Groups OD (450 nm) 0 d 1 d 2 d 3 d 4 d NC-mimic 0.35 ± 0.06 0.51 ± 0.05 1.10 ± 0.05 1.53 ± 0.04 1.90 ± 0.03 miR-200b-3p mimic 0.34 ± 0.04 0.40 ± 0.05 0.43 ± 0.04 0.53 ± 0.05 0.61 ± 0.04 t 0.600 2.694 18.124 27.050 44.687 P 0.581 0.054 < 0.001 < 0.001 < 0.001 miR-200b-3p mimic + oe-NC 0.31 ± 0.05 0.39 ± 0.04 0.42 ± 0.05 0.51 ± 0.03 0.59 ± 0.04 miR-200b-3p mimic + oe-FOSL2 0.34 ± 0.03 0.49 ± 0.02 0.82 ± 0.03 1.01 ± 0.05 1.35 ± 0.06 t 0.891 3.873 11.882 14.852 18.255 P 0.423 0.018 < 0.001 < 0.001 < 0.001 NC-inhibit 0.37 ± 0.08 0.52 ± 0.04 1.08 ± 0.04 1.47 ± 0.08 1.91 ± 0.04 miR-200b-3p inhibit 0.36 ± 0.03 0.69 ± 0.05 1.36 ± 0.05 1.71 ± 0.09 2.13 ± 0.08 t 0.203 4.599 10.046 3.452 4.260 P 0.849 0.010 0.002 0.026 0.13 miR-200b-3p inhibit + si-NC 0.36 ± 0.03 0.66 ± 0.04 1.31 ± 0.04 1.76 ± 0.03 2.14 ± 0.06 miR-200b-3p inhibit + si-FOSL2 0.37 ± 0.02 0.55 ± 0.03 1.13 ± 0.05 1.53 ± 0.04 2.01 ± 0.03 t 0.480 4.260 4.869 7.967 3.357 P 0.656 0.019 0.008 0.001 0.028 Table 7 Comparison of cell migration, invasion and EMT-related protein expression in each group (n = 3, x ± s) Groups Scratch repair rate (%) Numbers of cellpermeating septum(cells) N-cadherin Vimentin E-cadherin NC-mimic 51.31 ± 2.87 79.89 ± 7.03 1.02 ± 0.03 1.02 ± 0.01 0.80 ± 0.02 miR-200b-3p mimic 29.84 ± 3.21 36.97 ± 6.49 0.42 ± 0.03 0.51 ± 0.03 1.17 ± 0.02 t 8.636 7.770 24.495 27.934 22.658 P < 0.001 0.001 < 0.001 < 0.001 < 0.001 miR-200b-3p mimic + oe-NC 32.46 ± 3.11 40.59 ± 8.03 0.45 ± 0.04 0.47 ± 0.03 1.10 ± 0.04 miR-200b-3p mimic + oe-FOSL2 42.89 ± 3.98 64.28 ± 6.32 0.91 ± 0.03 0.83 ± 0.04 0.94 ± 0.03 t 3.577 4.015 15.935 12.471 5.543 P 0.023 0.016 < 0.001 < 0.001 < 0.001 NC-inhibit 49.79 ± 4.11 85.31 ± 4.86 1.02 ± 0.02 1.03 ± 0.01 0.89 ± 0.02 miR-200b-3p inhibit 71.16 ± 3.15 121.40 ± 9.35 1.40 ± 0.04 1.44 ± 0.03 0.38 ± 0.03 t 3.148 5.932 14.717 22.457 24.500 P 0.002 0.004 < 0.001 < 0.001 < 0.001 miR-200b-3p inhibit + si-NC 76.59 ± 2.62 122.59 ± 6.83 1.42 ± 0.05 1.42 ± 0.03 0.40 ± 0.02 miR-200b-3p inhibit + si-FOSL2 60.97 ± 3.28 105.18 ± 7.12 1.23 ± 0.03 1.29 ± 0.04 0.73 ± 0.03 t 6.466 3.056 5.644 4.503 15.853 P 0.003 0.038 0.001 0.011 < 0.001 Discussion miRNA is an endogenous non-coding RNA that exhibit a high degree of sequence and functional conservation, and affect downstream mRNA expression through post-transcriptional regulatory mechanisms. This regulatory process involves the specific binding of miRNA to the 3' untranslated region (3'UTR) of mRNA, which in turn affects mRNA stability, translational efficiency, or directly leads to the degradation of mRNAs, thereby regulating a variety of cancer-related processes, and playing an important role in the occurrence and development of many cancers, with great potential for diagnostics and therapy. miR-200b- 3p can perform different functions depending on the tumor type. In most cases, exhibits tumor suppressor effects that are down-regulated in cancerous tissues and cells. For example, Li et al.[ 14 ] found that miR-200b-3p expression in breast cancer tissues and cell lines was significantly lower than that in normal breast tissues and mammary epithelial cells. Xia et al.[ 15 ] identified that miR-200b-3p expression was downregulated in metastatic prostate cancer. In the present study, down regulation of miR-200b-3p expression in endometrial cancer cells was also confirmed. Recent studies have shown that miR-200b can inhibit the EMT process in endometrial cancer cells by promoting the expression of NKD2, which in turn regulates their invasive and migratory abilities.[ 9 ] Hong et al.[ 16 ]also demonstrated that miR-200b-3p can inhibit the migration and invasion of breast cancer cells by regulating the expression of ezrin-radixin-moesin protein. In addition miR-200b-3p can also act on genes such as microfiber-associated glycoprotein 2 (MAGP2), Mothers Against Decapentaplegic Homolog 2 (SMAD2) and high mobility group box 3 (HMGB3) to inhibit the life processes of tumor proliferation, apoptosis, invasion, and migration by silencing their mRNA expression. [ 10 ] In this study, overexpression of miR-200b-3p significantly inhibited the ability of EC cells for proliferation, migration and invasion, while inhibition of miR-200b-3p significantly promoted the ability of EC cells for proliferation, migration and invasion. Therefore, it is hypothesized that miR-200b-3p might be involved in EC progression as a tumor suppressor gene. FOSL2, a member of the Fos family and part of the AP-1 transcriptional complex, has been studied to be significantly up-regulated in expression in ovarian cancer tissues and to regulate ovarian cancer cell development by mediating the formation of inflammatory vesicles. [ 17 ] In this study, it is also found that FOSL2 expression is significantly increased in endometrial cancer cells, meaning that it may be involved in endometrial cancer progression as an oncogene. Some studies have found that FOSL2 can also act as a downstream target gene of miRNAs to affect cancer proliferation, migration and invasion, such as being targeted and inhibited by miR-143-3p to affect the proliferation and migration of myeloma,[ 18 ] and it can also promote the progression of colorectal cancer under the upstream regulation of miR-619-5p.[ 19 ] In this study, it is found that FOSL2 mRNA contains a binding site to miR-200b-3p by Starbase, therefore, FOSL2 is likely to be a potential target gene of miR-200b-3p, and this speculation is verified in this study by employing dual luciferase. Meanwhile, it is also observed that miR-200b-3p overexpression could inhibit the transcription and translation of FOSL2 in EC cells, and miR-200b-3p knockdown could have the opposite effect, further confirming that FOSL2 is one of the targets of miR-200b-3p, and that miR-200b-3p could negatively regulate FOSL2 expression in EC cells. In addition, the inhibitory effects of miR-200b-3p overexpression on the proliferation, migration and invasion of EC cells were able to be abrogated by FOSL2 overexpression, and the promotional effects of miR-200b-3p knockdown on the malignant phenotype of EC cells are able to be reversed by FOSL2 silencing. Thus, miR-200b-3p could inhibit the proliferation, migration and invasion of EC cells by targeting and suppressing FOSL2 expression. Tumor development is a complex process involving multiple factors, links and regulation, and abnormal expression in any link may lead to changes in protein expression, which in turn affects the value-added, invasive and migratory abilities of tumor cells and biological behaviors such as epithelial-mesenchymal transition (EMT), and ultimately has a significant impact on tumorigenesis, metastasis and prognosis. Epithelial-mesenchymal transition (EMT) refers to the loss of epithelial cells' original polarity and intercellular adhesion, and the acquisition of the ability to migrate and invade the stroma,[ 20 ] which is involved in the invasion and metastasis of a wide range of tumors, including EC.[ 21 , 22 ]EMT is characterized by a decrease in epithelial cell markers E-cadherin and β-catenin, and mesenchymal cell markers N- cadherin and Vimentin increase.[ 23 ] Some studies found that miR-200b-3p could inhibit EMT and thus tumor progression through Zinc finger E-box binding homology box 1/2 (ZEB1/2).[ 10 ] In triple-negative breast cancer, miR-200b-3p can target the Rho GDP Dissociation Inhibitor (RHOGDI) signaling pathway, thereby increasing CDH1 expression and EMT inhibition.[ 24 ] Xie et al. [ 25 ] also found that prostate leucine zipper PrLZ could further inhibit the expression of miR-200 family members by activating TGF-β1/p-smad2, thereby negatively regulating ZEB1 expression and causing EMT in prostate cancer. Yin et al.[ 26 ] found that FOSL2 promoted EMT, invasion and migration of non-small cell lung cancer cells by binding to the SNAI2 promoter to facilitate SNAI2 transcription. Some studies have confirmed that the miR-200 family and FOSL2 were involved in the regulation of EMT, however, whether miR-200b-3p regulates the involvement of FOSL2 in the EMT process of EC cells was unknown. In this study, miR-200b-3p overexpression is found to significantly inhibit the expression of N-cadherin and Vimentin and promote the expression of E-cadherin, meaning an inhibitory effect of miR-200b-3p on the EMT process in EC cells, and this effect could be abrogated by FOSL2 overexpression. Thus, the miR-200b-3p/FOSL2 axis may inhibit EC cell migration and invasion by inhibiting the EMT process. In summary, the expression of miR-200b-3p in endometrial cancer cells was down-regulated. It inhibits the proliferation, migration and invasion of endometrial cancer cells by regulating the EMT process, and its mechanism is related to its targeted negative regulation of FOSL2 expression. Targeting the miR-200b-3p/FOSL2 axis may become a new idea and a new target for the treatment of endometrial cancer. Future studies still need to further explore the specific mechanism of miR-200b-3p and FOSL2 in the occurrence and progression of endometrial cancer in animal models, as well as their interaction with other signaling pathways. Declarations · Ethics approval and consent to participate This study was approved by the Tianjin Fifth Central Hospital Ethics Committee, I confirmed that informed consent was obtained from all patients and their families , I confirmed all methods were carried out in accordance with Helsinki declaration . · Consent for publication All authors consent for publication · Availability of data and materials All data generated or analysed during this study are included in this published article · Competing interests not applicable · Funding Binhai New Area Health CommitteeTechnology projects Funding number :2023BWKQ003 Author Contribution Contributions: (I) Conception and design: Lijie He; (II) Administrative support: Zhe Han; (III) Provision of study materials or patients: Lijie He; (IV) Data analysis and interpretation: Jing Wang; (V) Manuscript writing: All authors; (VI) Final approval of manuscript: All authors.# Lijie He and Jing Wang these two authors contribute equally to this paper. 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Transcriptional regulation of PRKAR2B by miR-200b-3p/200c-3p and XBP1 in human prostate cancer. Biomed. Pharmacother . 124 , 109863. https://doi.org/10.1016/j.biopha.2020.109863 (2020). Hong, H. et al. MicroRNA-200b Impacts Breast Cancer Cell Migration and Invasion by Regulating Ezrin-Radixin-Moesin. Med. Sci. Monit. 22 , 1946–1952. https://doi.org/10.12659/msm.896551 (2016). Li, J., Zhou, L., Jiang, H., Lin, L. & Li, Y. Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes. Genes Genomics . 44 , 29–38. https://doi.org/10.1007/s13258-021-01152-6 (2022). Sun, X. et al. miR-143-3p inhibits the proliferation, migration and invasion in osteosarcoma by targeting FOSL2. Sci. Rep. 8 , 606. https://doi.org/10.1038/s41598-017-18739-3 (2018). Ma, W., Niu, Z., Han, D., Wang, B. & Wang, X. Circ-FAT1 Up-Regulates FOSL2 Expression by Sponging miR-619-5p to Facilitate Colorectal Cancer Progression. Biochem. Genet. 60 , 1362–1379. https://doi.org/10.1007/s10528-021-10148-6 (2022). Dedes, K. J., Wetterskog, D., Ashworth, A., Kaye, S. B. & Reis-Filho, J. S. Emerging therapeutic targets in endometrial cancer. Nat. Rev. Clin. Oncol. 8 , 261–271. https://doi.org/10.1038/nrclinonc.2010.216 (2011). Das, V., Bhattacharya, S., Chikkaputtaiah, C., Hazra, S. & Pal, M. The basics of epithelial-mesenchymal transition (EMT): A study from a structure, dynamics, and functional perspective. J. Cell. Physiol. 234 , 14535–14555. https://doi.org/10.1002/jcp.28160 (2019). Mirantes, C. et al. Epithelial-to-mesenchymal transition and stem cells in endometrial cancer. Hum. Pathol. 44 , 1973–1981. https://doi.org/10.1016/j.humpath.2013.04.009 (2013). Thiery, J. P. Epithelial-mesenchymal transitions in development and pathologies. Curr. Opin. Cell. Biol. 15 , 740–746. https://doi.org/10.1016/j.ceb.2003.10.006 (2003). Rhodes, L. V. et al. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4866332","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":354193407,"identity":"69fc72e1-a017-4643-a018-353e06d652b2","order_by":0,"name":"Lijie He#","email":"","orcid":"","institution":"Fifth Tianjin Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lijie","middleName":"","lastName":"He#","suffix":""},{"id":354193408,"identity":"f3e4c021-c439-4476-b3c5-be71097959c3","order_by":1,"name":"Jing Wang","email":"","orcid":"","institution":"Fifth Tianjin Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Wang","suffix":""},{"id":354193409,"identity":"6cb60d92-2b71-4383-b049-f6a03d70d054","order_by":2,"name":"zhe han","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAoUlEQVRIiWNgGAWjYBACAwYGZgaGCgk5eRK1nLEwNmwgSQtjW0UiwwFitZjznzE2+DlPIoGxgfnhoxvEaLFsOJac2LtNIo+dgc3YOIcohx1sPnyAd5tEMWMDD5s0cVoOMzYf/DtHIrHhANFajjEfTuZtIEnLGbZkY5ljEsaGzUT75fwZY8k3NXVy8uzNDx8TpQUBmElTPgpGwSgYBaMAHwAAUrAsxeoqi68AAAAASUVORK5CYII=","orcid":"","institution":"Fifth Tianjin Central Hospital","correspondingAuthor":true,"prefix":"","firstName":"zhe","middleName":"","lastName":"han","suffix":""}],"badges":[],"createdAt":"2024-08-06 07:15:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4866332/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4866332/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-00224-x","type":"published","date":"2025-05-06T15:57:08+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":64742321,"identity":"86a1ceb4-7406-4f28-a747-6e99f6b58f53","added_by":"auto","created_at":"2024-09-18 09:07:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":8890,"visible":true,"origin":"","legend":"\u003cp\u003eProtein level expression of FOSL2 in EC cells\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4866332/v1/09ebdd39fb0341adb821f0cd.jpg"},{"id":64742322,"identity":"78d8a529-7500-4d71-ba2d-9b1e0c6bd54d","added_by":"auto","created_at":"2024-09-18 09:07:47","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":31662,"visible":true,"origin":"","legend":"\u003cp\u003eFOSL2 is a downstream target gene of miR-200b-3p\u003c/p\u003e\n\u003cp\u003eA: Target binding site of miR-200b-3p with FOSL2 3'- UTR, B: Protein expression levels of FOSL2 in overexpression and knockdown constructs, C: Protein expression levels of FOSL2 in \u003cstrong\u003eeach group of cells\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4866332/v1/11e4c6bbcd6bcaea9fc48562.jpg"},{"id":64742325,"identity":"7da755c8-cb5a-4ffa-838e-c7ad5698308f","added_by":"auto","created_at":"2024-09-18 09:07:47","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2340120,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEffect of miR-200b-3p on proliferation, migration and invasion of endometrial cancer cells\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA: cell scratch assay to detect cell migration; B: Transwell assay to detect cell invasion; Western blot to detect the expression of EMT marker proteins in tumor tissues.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4866332/v1/d4c75ec02ae94c5c40d6ad52.jpg"},{"id":82537451,"identity":"a60edfba-b4ca-4cf9-9aab-f7e22bd6f175","added_by":"auto","created_at":"2025-05-12 16:06:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3456504,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4866332/v1/cea5d684-2362-4f99-9f7c-ce611423f30a.pdf"},{"id":64742329,"identity":"e5646d98-c17c-4e36-9fa8-5fdc605a0b09","added_by":"auto","created_at":"2024-09-18 09:07:48","extension":"xlsx","order_by":13,"title":"","display":"","copyAsset":false,"role":"supplement","size":979002,"visible":true,"origin":"","legend":"","description":"","filename":"XLSX.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4866332/v1/79e8a4253be2beaf30c3c24d.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mechanism of miR-200b-3p-induced FOSL2 inhibition of endometrial cancer cell proliferation and metastasis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndometrial cancer (EC) is a malignant tumor that occurs in the epithelial lining of the uterus in the female reproductive system, with adenocarcinoma being the most common, and its incidence is steadily increasing worldwide.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Early treatment of EC results in a relatively good prognosis, but patients with advanced or recurrent EC have a poorer clinical prognosis and a significantly lower survival rate, with 5-year survival rates of 44% and 37% in patients with pelvic and extra-pelvic metastases, respectively.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] As the only gynecologic malignancy with an increased mortality rate,[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] there is an urgent need for further exploration of the mechanisms of its development and progression. MicroRNAs (miRNAs) is a class of small non-coding RNA (ncRNA), usually composed of 19\u0026ndash;24 nucleotides, that can directly affect or regulate intracellular signaling pathways and indirectly influence the expression of tumor-associated proteins, thereby exerting antitumor effects or carcinogenesis.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] A variety of miRNA have been found to be closely related to endometrial cancer development and progression.[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Among them, miR-200b can affect cancer progression by regulating the EMT process in endometrial cancer cells.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] miR-200b-3p, which belongs to the miR-200b family, has also been found to inhibit the proliferation, invasion, and migration ability of a variety of tumors by inhibiting the expression of downstream mRNA.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] FOSL2, a member of the activator protein-1 (AP1) transcriptional family, is widely expressed in tissues, and is able to regulate growth, development, and immune responses, which play key roles in physiological and pathological processes.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Some studies have found that FOSL2 can act as a downstream target protein of miRNAs to regulate epithelial mesenchymal transition (EMT), metastasis, and other mediators of malignant tumor progression.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Although numerous studies have confirmed that miR-200b-3p and FOSL2 play important roles in the progression of some cancers, the roles of both in the development of endometrial cancer have not been clarified. Therefore, the aim of this study is to investigate the role of miR-200b-3p through its regulation of FOSL2 and its effect on the proliferation and metastasis of endometrial cancer cells, and to reveal its underlying molecular mechanisms.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1.1 Cells and Primary Reagents\u003c/h2\u003e \u003cp\u003eHuman endometrial cancer (HEC-1-A, RL95-2, Ishikawa) and human normal endometrial mesenchymal hEM15A are purchased from the Shanghai Cell Bank, Chinese Academy of Sciences. 0.25% trypsin, trypsin, DMEM medium, RPMI 1640 medium, and RIPA lysate are purchased from Promega, USA. TRIzol (Invitrogen, USA). miR-200b-3p inhibitor, FOSL2 inhibitor, and β-actin are purchased from Thermo Fisher Scientific, USA. N-cadherin inhibitor, Vimentin inhibitor and human E-cadherin inhibitor are purchased from CST, USA. miR-200b-3p mimic, miR-200b-3p inhibitor, si-FOSL2, oe-FOSL2 and the corresponding negative control are purchased from Ribobio, China. wild-type FOSL2 3'UTR (FOSL2-WT), mutant FOSL2 3'-UTR (FOSL2-WT) report vectors are purchased from Vigenebio, Shandong, China.The dual-luciferase reporter gene kit is purchased from Solarbio, USA. The CCK-8 reagent and the cell cycle kit are purchased from Beyotime Biotech Inc, Shanghai, China. Transwell chamber is purchased from Thermo, USA.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e1.2 Cell culture and cell transfection\u003c/h2\u003e \u003cp\u003eEndometrial cancer cell lines HEC-1-A, RL95-2, Ishikawa and human normal endometrial mesenchymal stromal cell line hEM15A were cultured in DMEM medium containing 10% fetal bovine serum (FBS) at 37℃ with 5% CO2 incubator. The HEC-1-A cell line was divided into 12 groups, and 3 replicate wells were set up in each group: NC-mimic (transfected with negative control NC mimic), miR-200b-3p mimic (transfected with miR-200b-3p mimic), NC-inhibit (transfected with negative control NC inhibit), miR-200b-3p inhibit group (transfected with miR-200b-3p inhibit), si-NC (transfected with negative control Si-NC), Si-FOSL2 (transfected with Si-FOSL2), oe-NC (transfected with negative control oe-NC), oe-FOSL2 group (oe-FOSL2), miR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-NC group (co-transfected with miR-200b-3p mimic and oe-NC), miR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-FOSL2 group (co-transfected with miR-200b-3p mimic and oe-FOSL2), miR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-NC group (co-transfected with miR-200b-3p inhibit and si-NC), miR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-FOSL2 group (co-transfected with miR-200b-3p inhibit and si-FOSL2). The miR-200b-3p mimic, miR-200b-3p inhibitor, si-FOSL2, oe-FOSL2, and the corresponding negative control were individually or co-transfected into HEC-1-A cells using the Lipofectamine 2000 kit according to the instructions. 48h later, the transfection efficiency was verified by real-time fluorescence quantitative PCR and Western blot to verify the transfection efficiency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e1.3 Real-time fluorescence quantitative PCR\u003c/h2\u003e \u003cp\u003eTotal RNA was extracted using TRIzol reagent, and the RNA concentration and OD260/OD280 ratio were detected using a NanoDrop ultraviolet spectrophotometer. 10 \u0026micro;g of RNA was taken and reverse transcribed into cDNA, and RT-qPCR was performed using SYBR Green Mix (Thermo Fisher Scientific, USA). β-actin was used as an internal reference, and the relative gene expression was calculated using the -ΔΔCT method. Three parallels were set in each group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e1.4 Western blot\u003c/h2\u003e \u003cp\u003eTotal protein was extracted using RIPA protein lysate containing 100\u0026times; Cocktail and 100\u0026times; PMSF, and protein concentration was determined by BCA protein assay kit. Proteins were electrophoretic transfered to PVDF membranes by 10% SDS-PAGE gel. After the transfer was completed, the membrane was closed with 5% skimmed milk for 1h at room temperature and incubated with the corresponding primary antibody at 4\u0026deg;C overnight. The membrane was washed with TBST buffer and incubated with the corresponding secondary antibody at room temperature for 1h. ECL reagent and chemiluminescence detection kit were used for blot analysis, β-actin was used as the internal control, and Image J v1.8 was used for blot analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e1.5 Bioinformatics analysis\u003c/h2\u003e \u003cp\u003eStarbase(\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://starbase.sysu.edu.cn/index.php\u003c/span\u003e\u003cspan address=\"http://starbase.sysu.edu.cn/index.php\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) was used to predict the potential binding site between miR-200b-3p and FOSL2 3'-UTR.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e1.6 Dual luciferase test\u003c/h2\u003e \u003cp\u003eHEC-1A cells were co-transfected with Lipofectamine 2000(miR-200b-3p mimic /NC mimic), wild-type FOSL2 3'UTR (FOSL2-WT), mutant FOSL2 3'-UTR (FOSL2-MUT). After 48h of transfection, luciferase activity was measured using Dual-Lucy Assay Kit.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e1.7 Cell proliferation assay\u003c/h2\u003e \u003cp\u003eCCK-8 was used to detect the proliferative activity of cells in each group. HEC-1A cells in logarithmic growth phase were prepared into a cell suspension of 5\u0026times;10\u003csup\u003e4\u003c/sup\u003e cells/mL, and 100 \u0026micro;L of the cell suspension was inoculated into 96-well plates and cultured at 37℃ with 5% CO2 for 2 to 3h. Subsequently, 10\u0026micro;L of CCK-8 reagent was added to each well, and the culture was continued for 2h. Absorbance values at 450nm were detected, and the data were recorded and the cell proliferation curves were plotted.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e1.8 Cell scratch assay\u003c/h2\u003e \u003cp\u003eCell migration was detected using the cell scratch assay. EC cells were inoculated in 6-well plates at a density of 1\u0026times;10\u003csup\u003e5\u003c/sup\u003e cells/well, and when the cell fusion reached more than 80%, a 200 \u0026micro;L tip was used to scratch vertically at the bottom of the well plates to form cell scratches. After completion of the scratch, the cells were rinsed with PBS to remove the suspended cells. Photographs were taken at 0h and 12h after scratching with a 10x field of view. The area of the scratch at each time point was analyzed using ImageJ software, and the mobility rate was calculated.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e1.9 Transwell Detection\u003c/h2\u003e \u003cp\u003eCell invasion was detected using the Transwell assay. HEC-1A cells were inoculated at a density of 1\u0026times;10\u003csup\u003e5\u003c/sup\u003e cells/well in the upper chamber of a small chamber containing 200 \u0026micro;L of serum-free medium, while 500 \u0026micro;L of medium containing 10% fetal bovine serum was added to the lower chamber. After 24 hours of incubation at 37\u0026deg;C with 5% CO2, cells remaining on the upper surface of the filter were removed, and cells migrating to the lower chamber were fixed using methanol and stained with crystal violet. Subsequently, five fields of view were randomly selected under a light microscope (10x objective), and the average cell number was calculated.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e1.10 Statistical analysis\u003c/h2\u003e \u003cp\u003eGraphPad Prism statistical software is applied to analyze the data and plot. Data in this study are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. t-test, one-way ANOVA and SNK-q test were used for comparison of measurement data. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 is considered as significant statistically difference.\u003c/p\u003e "},{"header":"Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003e2.1 miR-200b-3p mimic and FOSL2 expression in EC cells\u003c/h2\u003e\n \u003cp\u003eThe expression of miR-200b-3p is significantly down-regulated (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in EC cell lines compared to human normal endometrial cells. The lowest expression is found in HEC-1-A, which is selected for subsequent overexpression experiments. mRNA and protein expression of FOSL2 is significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in EC cell lines, as shown in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003emiR-200b-3p mRNA and protein expression in EC cell lines (n\u0026thinsp;=\u0026thinsp;3, x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFOSL2 mRNA\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFOSL2\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ehEM15A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHEC-1-A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRL95-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIshikawa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e792.900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e248.940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e181.759\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2 FOSL2 is a downstream target gene of miR-200b-3p\u003c/h2\u003e\n \u003cp\u003eThe existence of potential binding site of miR-200b-3p with FOSL2 3\u0026apos;-UTR is predicted using Starbase(Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA).Compared with the NC-mimic group, the expression of miR-200b-3p in the miR-200b-3p mimic group was significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared with the NC- inhibit group, and, miR-200b-3p expression in the miR-200b-3p inhibit group was significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Compared with the Si-NC group, FOSL2 mRNA and protein expression in the Si-FOSL2 group were significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared with the oe-NC group, the FOSL2 mRNA and protein expression in the oe-FOSL2 group were significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB and Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e ). Compared with the NC-mimic group, FOSL2 mRNA and protein expression in the miR-200b-3p mimic group were significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared with the miR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-NC group, FOSL2 mRNA and protein expression in the miR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-FOSL2 group were significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared with the NC-inhibit, FOSL2 mRNA and protein expression in the miR-200b-3p inhibit group were significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared with the miR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-NC group, FOSL2 mRNA and protein expression in the miR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si- FOSL2 group were significantly decreased(P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC). As a result of dual luciferase assay, Compared with the NC-mimic group, FOSL2-WT dual luciferase activity in the miR-200b-3p mimic group was significantly reduced (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared with the NC-inhibit group, FOSL2-WT dual luciferase activity in the miR-200b-3p inhibit group was significantly higher(P\u0026thinsp;\u0026lt;\u0026thinsp;0.001),( Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003emiR-200b-3p mRNA expression in each group of cells (n\u0026thinsp;=\u0026thinsp;3, x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eNC-mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003e34.293\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eNC-inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003e2.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003e33.607\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eExpression of FOSL2 mRNA and protein in each group of cells (n\u0026thinsp;=\u0026thinsp;3, x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eFOSL2 mRNA\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFOSL2\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esi-NC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esi-FOSL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e54.222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eoe-NC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eoe-FOSL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e2.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.557\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e23.105\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eExpression of FOSL2 mRNA and protein in each group of cells (n\u0026thinsp;=\u0026thinsp;3, x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFOSL2 mRNA\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFOSL2\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNC-mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.476\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-NC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-FOSL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.188\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.176\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNC-inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.656\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.732\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-NC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-FOSL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.090\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDual luciferase assay (n\u0026thinsp;=\u0026thinsp;3, x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFOSL2-WT\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFOSL2-MUT\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNC-mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.748\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.905\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNC-inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.931\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.144\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.893\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003e2.3 Effect of miR-200b-3p on endometrial cancer cell proliferation, migration and invasion\u003c/h2\u003e\n \u003cp\u003eCompared with the NC-mimic group, showed a significant decreased the cell proliferation activity, cell migration rate, and the number of membrane-penetrating cells in the miR-200b-3p mimic group were significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), the mRNA and protein expression levels of the epithelial markers, N-cadherin and Vimentin were significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and the mRNA and protein expression levels of mesenchymal marker were significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Compared with the miR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-NC group, cell proliferation activity, cell migration rate, and number of membrane-penetrating cells in the miR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-FOSL2 group were significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), the mRNA and protein expression levels of N-cadherin and Vimentin were significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and the mRNA and protein expression levels of E -cadherin\u0026apos;s mRNA and protein expression levels were significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Compared with the NC-inhibit group, the cell proliferation activity, cell migration rate, and number of membrane-penetrating cells in the miR-200b-3p inhibit group were significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), the mRNA and protein expression levels of N-cadherin and Vimentin were significantly increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and the mRNA and protein expression levels of E-cadherin were significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Compared with the miR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-NC group, the cell proliferative activity, cell migration rate, and the number of membrane-penetrating cells in the miR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-FOSL2 group were significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), mRNA and protein expression levels of N-cadherin and Vimentin were significant decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and the mRNA and protein expression levels of E-cadherin were significant increased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e and Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eProliferative activity of each group of cells detected by CCK-8 assay (n\u0026thinsp;=\u0026thinsp;3, x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"5\" align=\"left\"\u003e\n \u003cp\u003eOD (450 nm)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e0 d\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e1 d\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2 d\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3 d\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e4 d\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNC-mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.694\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.687\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.581\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-NC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-FOSL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.873\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.882\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.852\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.255\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.423\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNC-inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.046\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.452\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.260\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-NC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-FOSL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.869\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.967\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.357\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.656\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab7\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of cell migration, invasion and EMT-related protein expression in each group (n\u0026thinsp;=\u0026thinsp;3, x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eScratch repair rate (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumbers of cellpermeating septum(cells)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN-cadherin\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVimentin\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eE-cadherin\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNC-mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79.89\u0026thinsp;\u0026plusmn;\u0026thinsp;7.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.84\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.97\u0026thinsp;\u0026plusmn;\u0026thinsp;6.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.770\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.934\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.658\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-NC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.46\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.59\u0026thinsp;\u0026plusmn;\u0026thinsp;8.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p mimic\u0026thinsp;+\u0026thinsp;oe-FOSL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.89\u0026thinsp;\u0026plusmn;\u0026thinsp;3.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.28\u0026thinsp;\u0026plusmn;\u0026thinsp;6.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.935\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.471\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.543\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNC-inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.79\u0026thinsp;\u0026plusmn;\u0026thinsp;4.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.31\u0026thinsp;\u0026plusmn;\u0026thinsp;4.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.16\u0026thinsp;\u0026plusmn;\u0026thinsp;3.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e121.40\u0026thinsp;\u0026plusmn;\u0026thinsp;9.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.932\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.717\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.457\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.500\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-NC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e122.59\u0026thinsp;\u0026plusmn;\u0026thinsp;6.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiR-200b-3p inhibit\u0026thinsp;+\u0026thinsp;si-FOSL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e105.18\u0026thinsp;\u0026plusmn;\u0026thinsp;7.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.466\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.644\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.503\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.853\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003emiRNA is an endogenous non-coding RNA that exhibit a high degree of sequence and functional conservation, and affect downstream mRNA expression through post-transcriptional regulatory mechanisms. This regulatory process involves the specific binding of miRNA to the 3' untranslated region (3'UTR) of mRNA, which in turn affects mRNA stability, translational efficiency, or directly leads to the degradation of mRNAs, thereby regulating a variety of cancer-related processes, and playing an important role in the occurrence and development of many cancers, with great potential for diagnostics and therapy. miR-200b- 3p can perform different functions depending on the tumor type. In most cases, exhibits tumor suppressor effects that are down-regulated in cancerous tissues and cells. For example, Li et al.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] found that miR-200b-3p expression in breast cancer tissues and cell lines was significantly lower than that in normal breast tissues and mammary epithelial cells. Xia et al.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] identified that miR-200b-3p expression was downregulated in metastatic prostate cancer. In the present study, down regulation of miR-200b-3p expression in endometrial cancer cells was also confirmed. Recent studies have shown that miR-200b can inhibit the EMT process in endometrial cancer cells by promoting the expression of NKD2, which in turn regulates their invasive and migratory abilities.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Hong et al.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]also demonstrated that miR-200b-3p can inhibit the migration and invasion of breast cancer cells by regulating the expression of ezrin-radixin-moesin protein. In addition miR-200b-3p can also act on genes such as microfiber-associated glycoprotein 2 (MAGP2), Mothers Against Decapentaplegic Homolog 2 (SMAD2) and high mobility group box 3 (HMGB3) to inhibit the life processes of tumor proliferation, apoptosis, invasion, and migration by silencing their mRNA expression. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] In this study, overexpression of miR-200b-3p significantly inhibited the ability of EC cells for proliferation, migration and invasion, while inhibition of miR-200b-3p significantly promoted the ability of EC cells for proliferation, migration and invasion. Therefore, it is hypothesized that miR-200b-3p might be involved in EC progression as a tumor suppressor gene.\u003c/p\u003e \u003cp\u003eFOSL2, a member of the Fos family and part of the AP-1 transcriptional complex, has been studied to be significantly up-regulated in expression in ovarian cancer tissues and to regulate ovarian cancer cell development by mediating the formation of inflammatory vesicles. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] In this study, it is also found that FOSL2 expression is significantly increased in endometrial cancer cells, meaning that it may be involved in endometrial cancer progression as an oncogene. Some studies have found that FOSL2 can also act as a downstream target gene of miRNAs to affect cancer proliferation, migration and invasion, such as being targeted and inhibited by miR-143-3p to affect the proliferation and migration of myeloma,[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and it can also promote the progression of colorectal cancer under the upstream regulation of miR-619-5p.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] In this study, it is found that FOSL2 mRNA contains a binding site to miR-200b-3p by Starbase, therefore, FOSL2 is likely to be a potential target gene of miR-200b-3p, and this speculation is verified in this study by employing dual luciferase. Meanwhile, it is also observed that miR-200b-3p overexpression could inhibit the transcription and translation of FOSL2 in EC cells, and miR-200b-3p knockdown could have the opposite effect, further confirming that FOSL2 is one of the targets of miR-200b-3p, and that miR-200b-3p could negatively regulate FOSL2 expression in EC cells. In addition, the inhibitory effects of miR-200b-3p overexpression on the proliferation, migration and invasion of EC cells were able to be abrogated by FOSL2 overexpression, and the promotional effects of miR-200b-3p knockdown on the malignant phenotype of EC cells are able to be reversed by FOSL2 silencing. Thus, miR-200b-3p could inhibit the proliferation, migration and invasion of EC cells by targeting and suppressing FOSL2 expression.\u003c/p\u003e \u003cp\u003eTumor development is a complex process involving multiple factors, links and regulation, and abnormal expression in any link may lead to changes in protein expression, which in turn affects the value-added, invasive and migratory abilities of tumor cells and biological behaviors such as epithelial-mesenchymal transition (EMT), and ultimately has a significant impact on tumorigenesis, metastasis and prognosis. Epithelial-mesenchymal transition (EMT) refers to the loss of epithelial cells' original polarity and intercellular adhesion, and the acquisition of the ability to migrate and invade the stroma,[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] which is involved in the invasion and metastasis of a wide range of tumors, including EC.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]EMT is characterized by a decrease in epithelial cell markers E-cadherin and β-catenin, and mesenchymal cell markers N- cadherin and Vimentin increase.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Some studies found that miR-200b-3p could inhibit EMT and thus tumor progression through Zinc finger E-box binding homology box 1/2 (ZEB1/2).[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] In triple-negative breast cancer, miR-200b-3p can target the Rho GDP Dissociation Inhibitor (RHOGDI) signaling pathway, thereby increasing CDH1 expression and EMT inhibition.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] Xie et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] also found that prostate leucine zipper PrLZ could further inhibit the expression of miR-200 family members by activating TGF-β1/p-smad2, thereby negatively regulating ZEB1 expression and causing EMT in prostate cancer. Yin et al.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] found that FOSL2 promoted EMT, invasion and migration of non-small cell lung cancer cells by binding to the SNAI2 promoter to facilitate SNAI2 transcription. Some studies have confirmed that the miR-200 family and FOSL2 were involved in the regulation of EMT, however, whether miR-200b-3p regulates the involvement of FOSL2 in the EMT process of EC cells was unknown. In this study, miR-200b-3p overexpression is found to significantly inhibit the expression of N-cadherin and Vimentin and promote the expression of E-cadherin, meaning an inhibitory effect of miR-200b-3p on the EMT process in EC cells, and this effect could be abrogated by FOSL2 overexpression. Thus, the miR-200b-3p/FOSL2 axis may inhibit EC cell migration and invasion by inhibiting the EMT process.\u003c/p\u003e \u003cp\u003eIn summary, the expression of miR-200b-3p in endometrial cancer cells was down-regulated.\u003c/p\u003e \u003cp\u003eIt inhibits the proliferation, migration and invasion of endometrial cancer cells by regulating the EMT process, and its mechanism is related to its targeted negative regulation of FOSL2 expression. Targeting the miR-200b-3p/FOSL2 axis may become a new idea and a new target for the treatment of endometrial cancer. Future studies still need to further explore the specific mechanism of miR-200b-3p and FOSL2 in the occurrence and progression of endometrial cancer in animal models, as well as their interaction with other signaling pathways.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u0026middot; \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Tianjin Fifth Central Hospital Ethics Committee, I confirmed that \u003cstrong\u003einformed consent was obtained from all patients and their families\u003c/strong\u003e, I confirmed\u003cstrong\u003e\u0026nbsp;all methods were carried out in accordance with\u003c/strong\u003eHelsinki declaration\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026middot;\u003cstrong\u003e\u0026nbsp;Consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors consent for publication\u003c/p\u003e\n\u003cp\u003e\u0026middot; \u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article\u003c/p\u003e\n\u003cp\u003e\u0026middot;\u003cstrong\u003e\u0026nbsp;Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable\u003c/p\u003e\n\u003cp\u003e\u0026middot;\u003cstrong\u003e\u0026nbsp;Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBinhai New Area Health CommitteeTechnology projects\u003c/p\u003e\n\u003cp\u003eFunding number :2023BWKQ003\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eContributions: (I) Conception and design: Lijie He; (II) Administrative support: Zhe Han; (III) Provision of study materials or patients: Lijie He; (IV) Data analysis and interpretation: Jing Wang; (V) Manuscript writing: All authors; (VI) Final approval of manuscript: All authors.# Lijie He and Jing Wang these two authors contribute equally to this paper.\u003c/p\u003e\n\u003ch2\u003e\u0026nbsp;\u003c/h2\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCrosbie, E. 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HGF/MET Regulated Epithelial-Mesenchymal Transitions And Metastasis By FOSL2 In Non-Small Cell Lung Cancer. \u003cem\u003eOnco Targets Ther.\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e, 9227\u0026ndash;9237. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/OTT.S217595\u003c/span\u003e\u003cspan address=\"10.2147/OTT.S217595\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2019).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"miR-200b-3p, FOSL2, Endometrial cancer, Cell proliferation, Cell metastasis, EMT","lastPublishedDoi":"10.21203/rs.3.rs-4866332/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4866332/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective The purpose of this study was to investigate how miR-200b-3p inhibits the proliferation and metastasis of endometrial cancer cells by inducing the expression of FOSL2 in the AP1 transcription family.\u003c/p\u003e\n\u003cp\u003eMethods Endometrial cancer cell line HEC-1-A was divided into 12 groups: NC-mimic ( transfected with negative control NC mimic ), miR-200b-3p mimic ( transfected with miR-200b-3p mimic ), NC-suppress ( transfected with negative control NC inhibit ), miR-200b-3p inhibit group ( transfected with miR-200b-3p inhibit ), si-NC ( transfected with negative control Si-NC ), Si-FOSL2 ( transfected with Si-FOSL2 ), oe-NC ( transfected with negative control oe-NC ), oe-FOSL2 group ( oe-FOSL2 ), MiR-200b-3p mimic + oe-NC group ( co-transfected with miR-200b-3p mimic and oe-NC ), miR-200b-3p mimic + oe-FOSL2 group ( co-transfected with miR-200b-3p mimic and oe-FOSL2 ), miR-200b-3p inhibit + si-NC group ( co-transfected with miR-200b-3p inhibit and si-NC ), miR-200b-3p inhibit + si-FOSL2 group ( co-transfected with miR-200b-3p inhibit and si-FOSL2 ). Real-time fluorescence quantitative PCR, Western blot, CCK-8 assay, scratch test and Transwell assay were used to detect the expression of miR-200b-3p mRNA, FOSL2 mRNA and protein, cell proliferation, migration and invasion.\u003c/p\u003e\n\u003cp\u003eResults In endometrial cancer cell lines, the expression of miR-200b-3p was significantly down-regulated (P\u0026lt;0.05), while the expression of FOSssL2 was significantly up-regulated (P\u0026lt;0.05). Compared with NC-mimic group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic group was significantly decreased (P\u0026lt;0.05), and the expression of E-cadherin was significantly increased (P\u0026lt;0.05). The cell proliferation, migration rate and the number of transmembrane cells were significantly decreased (P\u0026lt;0.05). Compared with the miR-200b-3p mimic + oe-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic + oe-FOSL2 was significantly increased (P\u0026lt;0.05), the expression level of E-cadherin was significantly decreased (P\u0026lt;0.05), and the cell proliferation, migration rate and the number of transmembrane cells were significantly increased (P\u0026lt;0.05). Compared with NC-inhibit group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibit group was significantly increased (P\u0026lt;0.05), and the expression of E-cadherin was significantly decreased (P\u0026lt;0.05). The cell proliferation, migration rate and the number of transmembrane cells were significantly increased (P\u0026lt;0.05). Compared with the miR-200b-3p inhibit + si-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibit + si-FOSL2 was significantly decreased (P\u0026lt;0.05), and the expression of E-cadherin was significantly increased (P\u0026lt;0.05); the cell proliferation, migration rate and the number of transmembrane cells were significantly decreased (P\u0026lt;0.05)\u003c/p\u003e\n\u003cp\u003eConclusion The expression of miR-200b-3p in endometrial cancer cells is down-regulated, which can inhibit the proliferation, migration and invasion of endometrial cancer cells by regulating the EMT process, and its mechanism is related to its targeted negative regulation of FOSL2 expression.\u003c/p\u003e","manuscriptTitle":"Mechanism of miR-200b-3p-induced FOSL2 inhibition of endometrial cancer cell proliferation and metastasis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-18 09:07:42","doi":"10.21203/rs.3.rs-4866332/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-05T07:04:18+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-19T14:32:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-18T06:56:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"275115663805117450138469423108937742729","date":"2024-11-08T10:29:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"67835395537672470759129762254681562334","date":"2024-11-08T09:39:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-06T08:35:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"90759911036941397113020440688352015391","date":"2024-10-28T03:14:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-18T10:59:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-18T10:57:40+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-20T10:16:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-20T10:13:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-08-06T07:14:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d668e26f-d068-43b0-8ab7-77ed988271be","owner":[],"postedDate":"September 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":37641008,"name":"Biological sciences/Cancer"},{"id":37641009,"name":"Health sciences/Biomarkers"},{"id":37641010,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-05-12T15:59:51+00:00","versionOfRecord":{"articleIdentity":"rs-4866332","link":"https://doi.org/10.1038/s41598-025-00224-x","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-05-06 15:57:08","publishedOnDateReadable":"May 6th, 2025"},"versionCreatedAt":"2024-09-18 09:07:42","video":"","vorDoi":"10.1038/s41598-025-00224-x","vorDoiUrl":"https://doi.org/10.1038/s41598-025-00224-x","workflowStages":[]},"version":"v1","identity":"rs-4866332","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4866332","identity":"rs-4866332","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}