miR-141-3p affects apoptosis and migration of endometrial stromal cells by targeting KLF-12

article OA: closed CC0 ⤵ 18 in-corpus citations
AI-generated summary by claude@2026-06+body, 2026-06-10

miR-141-3p expression was altered in endometriosis samples, and it targeted KLF-12 to affect endometrial stromal cell apoptosis, proliferation, and migration.

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

AI-generated deep summary by claude@2026-06, 2026-06-10 · read from full text

This paper evaluated miR-141-3p expression in endometrial samples using real-time PCR and assessed Krüppel-like factor 12 (KLF-12) by western blot, with functional studies in ectopic endometrial stromal cells (ESCs). They found that miR-141-3p and KLF-12 were significantly different between paired ectopic and eutopic endometrial samples, and that miR-141-3p overexpression restrained proliferation and migration while promoting apoptosis of ectopic ESCs, with decreased miR-141-3p producing opposite effects; dual-luciferase reporter assays confirmed KLF-12 as a target. A major caveat explicitly implied by the study’s design is that the functional evidence comes from in vitro manipulation of ectopic ESCs rather than direct in vivo validation. This paper is centrally about endometriosis—specifically miR-141-3p regulation of apoptosis and migration in ectopic endometrial stromal cells via targeting KLF-12.

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

Abstract

Endometriosis is an estrogen-dependent disease that is characterized by pelvic pain and infertility. MicroRNAs have been shown to implicate in the progression of endometriosis. In our study, we used real-time PCR to evaluate the expression of miR-141-3p in endometrial samples. In addition, western blot analysis was used to assess the expression of Krüppel-like factor 12 (KLF-12). The proliferation and migration of ectopic endometrial stromal cells (ESCs) were determined by MTT assay and Transwell assay, respectively. Cell apoptosis was evaluated using a Cell Death Detection ELISA Plus kit. The results showed that miR-141-3p and KLF-12 were significantly different in paired ectopic and eutopic endometrial samples. miR-141-3p overexpression significantly restrained the proliferation and migration and promoted the apoptosis of ectopic ESCs, whereas a decreased level of miR-141-3p was associated with opposite results. Furthermore, dual-luciferase reporter assay confirmed that KLF-12 was a novel target of miR-141-3p, while it also decreased the effects of miR-141-3p on the proliferation, apoptosis, and migration of ectopic ESCs. Our data suggested that enhanced expression of miR-141-3p suppressed the proliferation and migration of ectopic ESCs and promoted their apoptosis via targeting KLF-12. Our results may provide a novel potential therapeutic target for the treatment of endometriosis.
Full text 10,388 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

Endometriosis is an estrogen-dependent disease that is characterized by pelvic pain and infertility. MicroRNAs have been shown to implicate in the progression of endometriosis. In our study, we used real-time PCR to evaluate the expression of miR-141-3p in endometrial samples. In addition, western blot analysis was used to assess the expression of Krüppel-like factor 12 (KLF-12). The proliferation and migration of ectopic endometrial stromal cells (ESCs) were determined by MTT assay and Transwell assay, respectively. Cell apoptosis was evaluated using a Cell Death Detection ELISA Plus kit. The results showed that miR-141-3p and KLF-12 were significantly different in paired ectopic and eutopic endometrial samples. miR-141-3p overexpression significantly restrained the proliferation and migration and promoted the apoptosis of ectopic ESCs, whereas a decreased level of miR-141-3p was associated with opposite results. Furthermore, dual-luciferase reporter assay confirmed that KLF-12 was a novel target of miR-141-3p, while it also decreased the effects of miR-141-3p on the proliferation, apoptosis, and migration of ectopic ESCs. Our data suggested that enhanced expression of miR-141-3p suppressed the proliferation and migration of ectopic ESCs and promoted their apoptosis via targeting KLF-12. Our results may provide a novel potential therapeutic target for the treatment of endometriosis. Similar content being viewed by others

References

Ahn JH, Choi YS, Choi JH (2015) Leptin promotes human endometriotic cell migration and invasion by up-regulating MMP-2 through the JAK2/STAT3 signaling pathway. Mol Hum Reprod 21(10):792–802 Anger DL, Foster WG (2008) The link between environmental toxicant exposure and endometriosis. Front Biosci 13:1578–1593 Bachmayr-Heyda A, Auer K, Sukhbaatar N, Aust S, Deycmar S, Reiner AT, Polterauer S, Dekan S, Pils D (2016) Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread. Oncotarget 7(26):39640–39653 Chuang TD, Khorram O (2018) Regulation of cell cycle regulatory proteins by microRNAs in uterine leiomyoma. Reprod Sci 1933719118768692 Dang DT, Pevsner J, Yang VW (2000) The biology of the mammalian Kruppel-like family of transcription factors. Int J Biochem Cell Biol 32(11–12):1103–1121 Du Y, Chen Y, Wang F, Gu L (2016) miR-137 plays tumor suppressor roles in gastric cancer cell lines by targeting KLF12 and MYO1C. Tumour Biol 37(10):13557–13569 Fang M, Huang W, Wu X, Gao Y, Ou J, Zhang X, Li Y (2019) MiR-141-3p suppresses tumor growth and metastasis in papillary thyroid cancer via targeting Yin Yang 1. Anat Rec (Hoboken) 302(2):258–268 Giudice LC (2010) Clinical practice. Endometriosis. N Engl J Med 362(25):2389–2398 Guan B, Li Q, Shen L, Rao Q, Wang Y, Zhu Y, Zhou XJ, Li XH (2016) MicroRNA-205 directly targets Kruppel-like factor 12 and is involved in invasion and apoptosis in basal-like breast carcinoma. Int J Oncol 49(2):720–734 Hawkins SM, Creighton CJ, Han DY, Zariff A, Anderson ML, Gunaratne PH, Matzuk MM (2011) Functional microRNA involved in endometriosis. Mol Endocrinol 25(5):821–832 Hou X, Yang L, Jiang X, Liu Z, Li X, Xie S, Li G, Liu J (2019) Role of microRNA-141-3p in the progression and metastasis of hepatocellular carcinoma cell. Int J Biol Macromol 128:331–339 Huang S, Wa Q, Pan J, Peng X, Ren D, Huang Y, Chen X, Tang Y (2017) Downregulation of miR-141-3p promotes bone metastasis via activating NF-kappaB signaling in prostate cancer. J Exp Clin Cancer Res 36(1):173 Jannot G, Simard MJ (2006) Tumour-related microRNAs functions in Caenorhabditis elegans. Oncogene. 25(46):6197–6201 Kaczynski J, Cook T, Urrutia R (2003) Sp1- and Kruppel-like transcription factors. Genome Biol 4(2):206 Khaliq OP, Murugesan S, Moodley J, Mackraj I (2018) Differential expression of miRNAs are associated with the insulin signaling pathway in preeclampsia and gestational hypertension. Clin Exp Hypertens:1–8 Kim SH, Park YY, Cho SN, Margalit O, Wang D, DuBois RN (2016) Kruppel-like factor 12 promotes colorectal cancer growth through early growth response protein 1. PLoS One 11(7):e0159899 Li JH, Zhang Z, Du MZ, Guan YC, Yao JN, Yu HY, Wang BJ, Wang XL, Wu SL, Li Z (2018) microRNA-141-3p fosters the growth, invasion, and tumorigenesis of cervical cancer cells by targeting FOXA2. Arch Biochem Biophys 657:23–30 Li W, Cui Y, Wang D, Wang Y, Wang L (2019) MiR-141-3p functions as a tumor suppressor through directly targeting ZFR in non-small cell lung cancer. Biochem Biophys Res Commun 509(3):647–656 Liu H, Zhang Z, Xiong W, Zhang L, Xiong Y, Li N, He H, Du Y, Liu Y (2017) Hypoxia-inducible factor-1alpha promotes endometrial stromal cells migration and invasion by upregulating autophagy in endometriosis. Reproduction 153(6):809–820 Miron L (2003) Systemic treatment of colorectal cancers—factual standards and perspectives. Rev Med Chir Soc Med Nat Iasi 107(4):752–758 Miska EA (2005) How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev 15(5):563–568 Moggio A, Pittatore G, Cassoni P, Marchino GL, Revelli A, Bussolati B (2012) Sorafenib inhibits growth, migration, and angiogenic potential of ectopic endometrial mesenchymal stem cells derived from patients with endometriosis. Fertil Steril 98(6):1521–30 e2 Nakamura Y, Migita T, Hosoda F, Okada N, Gotoh M, Arai Y, Fukushima M, Ohki M, Miyata S, Takeuchi K, Imoto I, Katai H, Yamaguchi T, Inazawa J, Hirohashi S, Ishikawa Y, Shibata T (2009) Kruppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression. Int J Cancer 125(8):1859–1867 Nothnick WB (2017) MicroRNAs and endometriosis: distinguishing drivers from passengers in disease pathogenesis. Semin Reprod Med 35(2):173–180 Oates AC, Pratt SJ, Vail B, Yan Y, Ho RK, Johnson SL, Postlethwait JH, Zon LI (2001) The zebrafish klf gene family. Blood 98(6):1792–1801 Ohlsson Teague EM, Van der Hoek KH, Van der Hoek MB, Perry N, Wagaarachchi P, Robertson SA, Print CG, Hull LM (2009) MicroRNA-regulated pathways associated with endometriosis. Mol Endocrinol 23(2):265–275 Painter JN, Anderson CA, Nyholt DR, Macgregor S, Lin J, Lee SH, Lambert A, Zhao ZZ, Roseman F, Guo Q, Gordon SD, Wallace L, Henders AK, Visscher PM, Kraft P, Martin NG, Morris AP, Treloar SA, Kennedy SH, Missmer SA, Montgomery GW, Zondervan KT (2011) Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nat Genet 43(1):51–54 Rapado-Gonzalez O, Majem B, Muinelo-Romay L, Alvarez-Castro A, Santamaria A, Gil-Moreno A, Lopez-Lopez R, Suarez-Cunqueiro MM (2018) Human salivary microRNAs in cancer. J Cancer 9(4):638–649 Rekker K, Saare M, Roost AM, Kaart T, Soritsa D, Karro H, Soritsa A, Simon C, Salumets A, Peters M (2015) Circulating miR-200-family micro-RNAs have altered plasma levels in patients with endometriosis and vary with blood collection time. Fertil Steril 104(4):938–946 e2 Shen X, Hu Y, Jiang Y, Liu H, Zhu L, Jin X, Shan H, Zhen X, Sun L, Yan G, Sun H (2013) Kruppel-like factor 12 negatively regulates human endometrial stromal cell decidualization. Biochem Biophys Res Commun 433(1):11–17 Suda S, Rai T, Sohara E, Sasaki S, Uchida S (2006) Postnatal expression of KLF12 in the inner medullary collecting ducts of kidney and its trans-activation of UT-A1 urea transporter promoter. Biochem Biophys Res Commun 344(1):246–252 Suske G, Bruford E, Philipsen S (2005) Mammalian SP/KLF transcription factors: bring in the family. Genomics 85(5):551–556 Ultimo S, Zauli G, Martelli AM, Vitale M, McCubrey JA, Capitani S, Neri LM (2018) Cardiovascular disease-related miRNAs expression: potential role as biomarkers and effects of training exercise. Oncotarget. 9(24):17238–17254 Vandenboom Ii TG, Li Y, Philip PA, Sarkar FH (2008) MicroRNA and cancer: tiny molecules with major implications. Curr Genomics 9(2):97–109 Wang L, Chen YJ, Xu K, Xu H, Shen XZ, Tu RQ (2014) Circulating microRNAs as a fingerprint for endometrial endometrioid adenocarcinoma. PLoS One 9(10):e110767 Wang N, Li P, Liu W, Lu Z, Feng J, Zeng X, Yang J, Wang Y, Zhao W (2018) miR-141-3p suppresses proliferation and promotes apoptosis by targeting GLI2 in osteosarcoma cells. Oncol Rep 39(2):747–754 Zhang Q, Zhang H, Jiang Y, Xue B, Diao Z, Ding L, Zhen X, Sun H, Yan G, Hu Y (2015) MicroRNA-181a is involved in the regulation of human endometrial stromal cell decidualization by inhibiting Kruppel-like factor 12. Reprod Biol Endocrinol 13(1):23 Zhou X, Wu W, Zeng A, Nie E, Jin X, Yu T, Zhi T, Jiang K, Wang Y, Zhang J, You Y (2017) MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53. Oncotarget 8(41):71080–71094 Author information Authors and Affiliations Contributions Yiwei Zhang and Juan Yan conceived and designed the study; Yiwei Zhang, Juan Yan, and Xiaowei Pan conducted experiments and collected the data; Yiwei Zhang and Juan Yan analyzed and interpreted the experiments results; Yiwei Zhang wrote the first draft of the manuscript; Yiwei Zhang, Juan Yan, and Xiaowei Pan revised the paper. All authors contributed to and approved the final manuscript. Corresponding author Ethics declarations The hospital ethics committee approved this study. Conflict of interest The authors declare that they have no conflict of interest. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Highlights 1. miR-141-3p is obviously decreased in endometriosis. 2. KLF-12 is significantly upregulated in endometriosis. 3. Restoration of miR-141-3p expression in ectopic ESCs inhibits cellular proliferation and migration. 4. Restoration of miR-141-3p expression in ectopic ESCs induces the apoptosis in ectopic ESCs. 5. KLF-12 is directly regulated by miR-141-3p. 6. KLF-12 reverses the miR-141-3p-induced suppression of cell proliferation and migration. 7. KLF-12 inhibits the miR-141-3p-mediated induction of cell apoptosis. Rights and permissions About this article Cite this article Zhang, Y., Yan, J. & Pan, X. miR-141-3p affects apoptosis and migration of endometrial stromal cells by targeting KLF-12. Pflugers Arch - Eur J Physiol 471, 1055–1063 (2019). https://doi.org/10.1007/s00424-019-02283-2 Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00424-019-02283-2

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

MeSH descriptors

Adult Stem Cells Apoptosis Cell Movement Endometrium Kruppel-Like Transcription Factors MicroRNAs Adult Adult Stem Cells Adult Stem Cells Cell Proliferation Cells, Cultured Endometrium Endometrium Female Humans Kruppel-Like Transcription Factors Kruppel-Like Transcription Factors MicroRNAs MicroRNAs

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 (43)

Cited by (19)

Source provenance

europepmc
last seen: 2026-08-05T06:13:34.187606+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:22:48.502547+00:00
unpaywall
last seen: 2026-08-05T06:45:03.150373+00:00
License: CC0 · commercial use OK