Dysregulation of hsa-miR-199a-5p and MAP3K11 in Endometriosis: An Association Study

OA: closed CC0
Full text JSON View on OpenAlex View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite+body, 2026-07-17 ⓘ

This study found that both hsa-miR-199a-5p and MAP3K11 were significantly upregulated in the peripheral blood mononuclear cells of women with endometriosis compared to controls.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by qwen3.7-flash, 2026-08-12 · read from full text ⓘ

This study investigated the expression levels of hsa-miR-199a-5p and its predicted target gene MAP3K11 in peripheral blood mononuclear cells from 40 women with endometriosis compared to 40 healthy controls. Quantitative real-time PCR analysis revealed that both genes were significantly upregulated in the patient group, showing a 6.6-fold and 9.2-fold increase respectively. Although a weak negative correlation was observed between the two molecules, it was not statistically significant, suggesting an indirect or post-transcriptional regulatory relationship rather than direct targeting. This paper is centrally about endometriosis — specifically examining circulating biomarkers associated with the disease pathology.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Full text 12,593 characters · extracted from oa-doi-fallback · 6 sections · click to expand

Abstract

Background Endometriosis is a gynecological disorder that affects a large number of women worldwide, with several complications including chronic pelvic pain, infertility, and reduced health. Considering the MAPK signaling pathway is involved in endometriosis, we examined the hsa-miR-199a-5p and its predicted target gene, MAP3K11, expression levels to investigate an association between their concurrent dysregulation and endometriosis and to assess their expression changes in peripheral blood mononuclear cells (PBMCs).

Methods

The sequences of hsa-miR-199a-5p and its target gene, MAP3K11, were obtained by using TargetScan and miRDB databases. Blood samples were collected from 40 women diagnosed with endometriosis and 40 age-matched healthy controls. Quantitative real-time PCR was conducted to assess the expression levels of the genes, and GAPDH and U6 genes were used as internal control genes.

Results

We observed a notable increase in the expression levels of both hsa-miR-199a-5p and MAP3K11 genes, 6.6-times and 9.2-times, respectively, in the patient group compared with healthy controls. Despite increased expression levels of the studied genes, a weak, non-significant negative correlation was observed between them (r = − 0.15).

Conclusions

These results indicate co-upregulation of both genes in PBMCs, suggesting that their interaction may involve an indirect or post-transcriptional relationship between hsa-miR-199a-5p and MAP3K11. Overall, the findings support that dysregulated circulating miRNAs and their target genes may be associated with endometriosis. Similar content being viewed by others Data Availability No datasets were generated or analysed during the current study.

References

Chen G, et al. Diagnostic value of the combination of circulating serum miRNAs and CA125 in endometriosis. Med (Baltim). 2023;102(48):e36339. https://doi.org/10.1097/MD.0000000000036339. Christ JP, et al. Incidence, prevalence, and trends in endometriosis diagnosis: a United States population-based study from 2006 to 2015. Am J Obstet Gynecol. 2021;225(5):500. https://doi.org/10.1016/j.ajog.2021.06.067 Matías-González Y, et al. Stigma and social support and their impact on quality of life and self-esteem among women with endometriosis in Latin-America and the Caribbean. PLOS Glob Public Health. 2022;2(12):e0001329. https://doi.org/10.1371/journal.pgph.0001329. Burney RO. The genetics and biochemistry of endometriosis. Curr Opin Obstet Gynecol. 2013;25(4):280–6. https://doi.org/10.1097/GCO.0b013e3283620f7b. Giudice LC, et al. Endometriosis in the era of precision medicine and impact on sexual and reproductive health across the lifespan and in diverse populations. FASEB J. 2023;37(9):e23130. https://doi.org/10.1096/fj.202300156R. Lamceva J, Uljanovs R, Strumfa I. The main theories on the pathogenesis of endometriosis. Int J Mol Sci. 2023;24(5):4254. https://doi.org/10.3390/ijms24054254. Wang Y, Nicholes K, Shih I-M. The origin and pathogenesis of endometriosis. Annu Rev Pathol. 2020;15:71–95. https://doi.org/10.1146/annurev-pathmechdis-012419-032654. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511–9. https://doi.org/10.1016/j.fertnstert.2012.06.029. Nnoaham KE, et al. Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study. Fertil Steril. 2012;98(3):692–e7015. https://doi.org/10.1016/j.fertnstert.2012.04.039. Agrawal S, et al. The miRNA mirage: how close are we to finding a non-invasive diagnostic biomarker in endometriosis? A systematic review. Int J Mol Sci. 2018;19(2):599. https://doi.org/10.3390/ijms19020599. Sourial S, Tempest N, Hapangama DK. Theories on the pathogenesis of endometriosis. Int J Reprod Med. 2014;2014:179515. https://doi.org/10.1155/2014/179515. Marquardt RM, et al. Progesterone and estrogen signaling in the endometrium: what goes wrong in endometriosis? Int J Mol Sci. 2019;20(15):3822. https://doi.org/10.3390/ijms20153822. Donnez O, et al. Induction of endometriotic nodules in an experimental baboon model mimicking human deep nodular lesion. Fertil Steril. 2013;99(3):783–9. https://doi.org/10.1016/j.fertnstert.2012.10.030. e5. Lv X, Chen P, Liu W. Down regulation of MiR-93 contributes to endometriosis through targeting MMP3 and VEGFA. Am J Cancer Res. 2015;5(5):1706–17. Asghari S, et al. Endometriosis: Perspective, lights, and shadows of etiology. Biomed Pharmacother. 2018. https://doi.org/10.1016/j.biopha.2018.06.130. 106:163 – 74. Raja MHR, et al. Endometriosis, infertility and MicroRNA’s: A review. J Gynecol Obstet Hum Reprod. 2021;50(9):102157. https://doi.org/10.1016/j.jogoh.2021.102157. Vanhie A, et al. Circulating microRNAs as non-invasive biomarkers in endometriosis diagnosis—a systematic review. Biomedicines. 2024;12(4):888. https://doi.org/10.3390/biomedicines12040888. Li X, et al. MiR-136-5p in cancer: Roles, mechanisms, and chemotherapy resistance. Gene. 2024;909:148265. https://doi.org/10.1016/j.gene.2024.148265. Dai L, et al. MiR-199a inhibits the angiogenic potential of endometrial stromal cells under hypoxia by targeting HIF-1α/VEGF pathway. Int J Clin Exp Pathol. 2015;8(5):4735–44. Li Y, et al. Hsa-miR-199a-5p suppresses non-small cell lung cancer via targeting MAP3K11. J Cancer. 2019;10(11):2472–8. https://doi.org/10.7150/jca.30270. Wang WT, et al. Circulating microRNAs identified in a genome-wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis. J Clin Endocrinol Metab. 2013;98(1):281–9. https://doi.org/10.1210/jc.2012-2415. Maged AM, et al. Diagnostic accuracy of serum miR-122 and miR‐199a in women with endometriosis. Int J Gynaecol Obstet. 2018;141(1):14–9. https://doi.org/10.1002/ijgo.12433. Hsu CY, et al. miRNA-199a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis. J Pathol. 2014;232(3):330–43. https://doi.org/10.1002/path.4295. Agarwal V, et al. Predicting effective microRNA target sites in mammalian mRNAs. eLife. 2015;4:e05005. https://doi.org/10.7554/eLife.05005. Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2020;48(D1):D127–31. https://doi.org/10.1093/nar/gkz1020. Kuleshov MV, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44(1):90–7. . . https://doi.org/10.1093/nar/gkw377 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156–9. https://doi.org/10.1006/abio.1987.9999. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33(20):e179. https://doi.org/10.1093/nar/gni178. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 – ∆∆CT method. Methods. 2001;25(4):402–8. https://doi.org/10.1006/meth.2001.1262. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009;55(4):611–22. Benz F, et al. U6 is unsuitable for normalization of serum miRNA levels in patients with sepsis or liver fibrosis. Exp Mol Med. 2013;45:e42. Lou G, et al. Differential distribution of U6 (RNU6-1) expression in human carcinoma tissues demonstrates the requirement for caution in the internal control gene selection for microRNA quantification. Int J Mol Med. 2015;36(5):1401–8. Duan ZY, et al. U6 can be used as a housekeeping gene for urinary sediment miRNA studies of IgA nephropathy. Sci Rep. 2018;8:10875. Peletto S, et al. Evaluation of internal reference genes for quantitative expression analysis by real-time PCR in ovine whole blood. Int J Mol Sci. 2011;12(11):7732–47. Hieronymus K, et al. Validation of reference genes for whole blood gene expression analysis in cord blood of preterm and full-term neonates and peripheral blood of healthy adults. BMC Genomics. 2021;22:489. Ruxton GD. The unequal variance t-test is an underused alternative to Student’s t-test and the Mann–Whitney U test. Behav Ecol. 2006;17(4):688–90. https://doi.org/10.1093/beheco/ark016. He S, et al. MiR-199a-3p/5p participated in TGF-β and EGF induced EMT by targeting DUSP5/MAP3K11 in pterygium. J Transl Med. 2020;18(1):332. https://doi.org/10.1186/s12967-020-02514-5. Lu TX, Rothenberg ME, MicroRNA. J Allergy Clin Immunol. 2018;141(4):1202–7. https://doi.org/10.1016/j.jaci.2017.08.034. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–. https://doi.org/10.1016/j.cell.2009.01.002. 33. Pu M, et al. Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression. Cell Mol Life Sci. 2019;76(3):441–51. https://doi.org/10.1007/s00018-018-2940-9. Diener C, et al. The miRNA-target interactions: An underestimated intricary. Nucleic Acids Res. 2023;52(4):1544–57. https://doi.org/10.1093/nar/gkad1142. Filigheddu N, et al. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. Biomed Res Int. 2010;2010:369549. https://doi.org/10.1155/2010/369549. Liu Y, Wang J, Zhang X. An update on the multifaceted role of NF-kappaB in endometriosis. Int J Biol Sci. 2022;18(11):4400–13. https://doi.org/10.7150/ijbs.72704. Xiong H, et al. MicroRNA–199a/b–5p inhibits endometrial cancer cell metastasis and invasion by targeting FAM83B in the epithelial–to–mesenchymal transition signaling pathway. Mol Med Rep. 2021;23(5):332. https://doi.org/10.3892/mmr.2021.11971. Bora G, Yaba A. The role of mitogen-activated protein kinase signaling pathway in endometriosis. J Obstet Gynaecol Res. 2021;47(5):1610–23. https://doi.org/10.1111/jog.14692. Schoeman EM, et al. Identification of plasma protein biomarkers for endometriosis and the development of statistical models for disease diagnosis. Hum Reprod. 2025;40(2):270–9. https://doi.org/10.1093/humrep/deae278. Zhang Y, et al. Research advances in endometriosis-related signaling pathways: A review. Biomed Pharmacother. 2023;164:114945. https://doi.org/10.1016/j.biopha.2023.114945. Oskouei BS, Asadi Z, Esfahlan RJ. Non-invasive blood tests for earlier diagnosis and treatment of endometriosis. J Reprod Immunol. 2025;104521. https://doi.org/10.1016/j.jri.2025.104521.

Acknowledgements

The authors thank all participants in this study, and we especially thank the University of Guilan for supporting our study. Funding This research did not receive any grant from funding agencies. Author information Authors and Affiliations Contributions Mahdis Saffarhamidi conducted the experiments. Soheila Talesh Sasani and Zivar Salehi designed the study. Fereshteh Fakor examined the participants ' clinicopathological characteristics and validated their features. Mahdis Saffarhamidi and Soheila Talesh Sasani analyzed the data. Soheila Talesh Sasani and Mahdis Saffarhamidi reviewed the literature and wrote the manuscript. All authors read and approved the final manuscript. Corresponding author Ethics declarations Ethics Approval This study received approval ID by the Research Ethics Committees of the University of Guilan (IR.GUILAN.REC.1403.085), and all steps of the study were conducted in line with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Competing interests The authors declare no competing interests. Consent to Participate Informed consent was obtained from all people who participated in our research. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Saffarhamidi, M., Sasani, S.T., Fakor, F. et al. Dysregulation of hsa-miR-199a-5p and MAP3K11 in Endometriosis: An Association Study. Curr Genet Med Rep 14, 21 (2026). https://doi.org/10.1007/s40142-026-00254-5 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s40142-026-00254-5

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (86)

Source provenance

crossref
last seen: 2026-08-21T06:37:00.003946+00:00
openalex
last seen: 2026-10-12T06:08:43.041439+00:00
unpaywall
last seen: 2026-10-19T06:34:38.229974+00:00
License: CC0 · commercial use OK