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Archives of Gynecology and Obstetrics

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Open Access 01-03-2020 | Endometriosis | General Gynecology

microRNA-141 inhibits TGF-β1-induced epithelial-to-mesenchymal transition through inhibition of the TGF-β1/SMAD2 signalling pathway in endometriosis

Authors: Sixue Wang, Mengmeng Zhang, Tingting Zhang, Juan Deng, Xiaomeng Xia, Xiaoling Fang

Published in: Archives of Gynecology and Obstetrics | Issue 3/2020

Abstract

Purpose

Recent studies have demonstrated the differential expression of micro(mi)RNAs in endometriosis. Previously, we reported the low expression of miR-141 in patients with this disease. Epithelial-to-mesenchymal transition (EMT) and the transforming growth factor-beta1 (TGF-β1)-induced SMAD2 signalling pathway are central to tumour proliferation and invasion. However, the role of miR-141 in regulating the TGF-β1/SMAD2 signalling pathway and the associated EMT to be elucidated.

Methods

The levels of TGF-β1/SMAD2 signalling and EMT markers expression in eutopic and ectopic endometria of endometriosis were determined by immunohistochemistry and western blot analyses. MiR-141 expression was analysed by quantitative reverse-transcription polymerase chain reaction. Cellular invasion and proliferation were determined by transwell and CCK-8 assays, respectively. Functional assay of miR-141 was performed using plasmid and shRNA transfection methods.

Result

The presence of miR-141, EMT, and TGF-β1/SMAD2 signalling markers were detected in eutopic and ectopic endometria of endometriosis. TGF-β1-induced EMT in Ishikawa (ISK) cells by activating the SMAD2 signalling pathway, whereas miR-141 inhibited the TGF-β1-induced EMT, proliferation and invasion abilities of these cells.

Conclusion

These data identify miR-141 as a novel driver of EMT in endometriosis, implicates the link between miR-141 and TGF-β1/SMAD2 signalling pathway in the context of endometriosis, and underscore the role of EMT in the development of endometriosis.

Kvaskoff M, Mu F, Terry KL et al (2015) Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update 21:500–516CrossRef

Giudice LC, Kao LC (2004) Endometriosis. Lancet 364:1789–1799CrossRef

Anglesio MS, Papadopoulos N, Ayhan A et al (2017) Cancer-associated mutations in endometriosis without cancer. N Engl J Med 376:1835–1848CrossRef

Choi J, Jo M, Lee E et al (2017) Aberrant PTEN expression in response to progesterone reduces endometriotic stromal cell apoptosis. Reproduction 153:11–21CrossRef

Kurman RJ, Shih I-M (2011) Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer—shifting the paradigm. Hum Pathol 42:918–931CrossRef

Han SJ, Jung SY, Wu S-P et al (2015) Estrogen receptor β modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis. Cell 163:960–974CrossRef

Budi EH, Duan D, Derynck R (2017) Transforming growth factor-beta receptors and smads: regulatory complexity and functional versatility. Trends Cell Biol 27:658–672CrossRef

Lambert AW, Pattabiraman DR, Weinberg RA (2017) Emerging biological principles of metastasis. Cell 168:670–691CrossRef

Shen M, Liu X, Zhang H et al (2016) Transforming growth factor beta1 signaling coincides with epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis in mice. Hum Reprod 31:355–369CrossRef

10.

Guasch G, Schober M, Pasolli HA et al (2007) Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell 12:313–327CrossRef

11.

Cesi V, Casciati A, Sesti F et al (2011) TGFbeta-induced c-Myb affects the expression of EMT-associated genes and promotes invasion of ER+ breast cancer cells. Cell Cycle 10:4149–4161CrossRef

12.

Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7:131–142CrossRef

13.

Papageorgis P, Lambert AW, Ozturk S et al (2010) Smad signaling is required to maintain epigenetic silencing during breast cancer progression. Cancer Res 70:968–978CrossRef

14.

Matsuzaki S, Darcha C (2012) Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis. Hum Reprod 27:712–721CrossRef

15.

Braza-Boils A, Mari-Alexandre J, Gilabert J et al (2014) MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors. Hum Reprod 29:978–988CrossRef

16.

Ohlsson Teague EMC, Print CG, Hull ML (2010) The role of microRNAs in endometriosis and associated reproductive conditions. Hum Reprod Update 16:142–165CrossRef

17.

Thomou T, Mori MA, Dreyfuss JM et al (2017) Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature 542:450–455CrossRef

18.

Gregory PA, Bert AG, Paterson EL et al (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10:593–601CrossRef

19.

Sugiyama K, Kajiyama H, Shibata K et al (2014) Expression of the miR200 family of microRNAs in mesothelial cells suppresses the dissemination of ovarian cancer cells. Mol Cancer Ther 13:2081–2091CrossRef

20.

Petrocca F, Visone R, Onelli MR et al (2008) E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13:272–286CrossRef

21.

Burk U, Schubert J, Wellner U et al (2008) A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep 9:582–589CrossRef

22.

Papagiannakopoulos T, Shapiro A, Kosik KS (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res 68:8164–8172CrossRef

23.

Zhang M, Wang S, Tang L et al (2019) Downregulated circular RNA hsa_circ_0067301 regulates epithelial-mesenchymal transition in endometriosis via the miR-141/Notch signaling pathway. Biochem Biophys Res Commun 514:71–77CrossRef

24.

Wu J-W, Hu M, Chai J et al (2001) Crystal structure of a phosphorylated Smad2: recognition of phosphoserine by the MH2 domain and insights on smad function in TGF-β signalling. Mol Cell 8:1277–1289CrossRef

25.

Guo S-W (2009) Epigenetics of endometriosis. Mol Hum Reprod 15:587–607CrossRef

26.

Du Y, Zhang Z, Xiong W, et al. (2018) Estradiol promotes EMT in endometriosis via MALAT1/miR200s sponge function. Reproduction 157:179–188

27.

Guay S, Akoum A (2007) Stable inhibition of interleukin 1 receptor type II in Ishikawa cells augments secretion of matrix metalloproteinases: possible role in endometriosis pathophysiology. Reproduction 134:525–534CrossRef

28.

Kim BG, Yoo J-Y, Kim TH et al (2015) Aberrant activation of signal transducer and activator of transcription-3 (STAT3) signaling in endometriosis. Hum Reprod 30:1069–1078CrossRef

29.

Kim SH, Lee HW, Kim YH et al (2009) Down-regulation of p21-activated kinase 1 by progestin and its increased expression in the eutopic endometrium of women with endometriosis. Hum Reprod 24:1133–1141CrossRef

Title: microRNA-141 inhibits TGF-β1-induced epithelial-to-mesenchymal transition through inhibition of the TGF-β1/SMAD2 signalling pathway in endometriosis
Authors: Sixue Wang
Mengmeng Zhang
Tingting Zhang
Juan Deng
Xiaomeng Xia
Xiaoling Fang
Publication date: 01-03-2020
Publisher: Springer Berlin Heidelberg
Keyword: Endometriosis
Published in: Archives of Gynecology and Obstetrics / Issue 3/2020
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-019-05429-w

At a glance: The STEP trials

Springer Medicine

microRNA-141 inhibits TGF-β1-induced epithelial-to-mesenchymal transition through inhibition of the TGF-β1/SMAD2 signalling pathway in endometriosis

Abstract

Purpose

Methods

Result

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Result

Conclusion

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