{"paper_id":"98dbd981-7ca5-4735-9f6f-4ed5e9ba7dd4","body_text":"Abstract\nEndometriosis (Ems) is a common gynecological disease with the characteristics of infertility, pelvic pain, and sexual intercourse difficulty. Our present study aimed to investigate the effect of miR-199a-5p on cell mobility and epithelial-mesenchymal transition (EMT) in Ems. Ectopic endometrial stromal cells (EcSCs) and control endometrial stromal cells (CSCs) were isolated in our in vitro experiments. The level of miR-199a-5p in EcSCs was found much lower than that in CSCs. Besides, miR-199a-5p mimic suppressed the invasion and migration ability of EcSCs. At the same time, EMT was also found to be suppressed by miR-199a-5p mimic in EcSCs. Our further bioinformatics analysis and luciferase reporter assay revealed that ZEB1, a marker of EMT, was a direct target of miR-199a-5p. In addition, the combination of pcDNA3.1-ZEB1 weakened the inhibiting effect of miR-199a-5p mimic on the mobility and EMT of EcSCs. What is more, the PI3K/Akt/mTOR signal pathway was demonstrated to be inactivated by miR-199a-5p mimic. And then, the inducer of PI3K/Akt/mTOR signal pathway, IGF-1, abolished the effect of miR-199a-5p mimic on Ems progression. At last, an Ems rat model was established, and we found that miR-199a-5p agomir effectively suppressed the expression of vascular endothelial growth factor (VEGF) and EMT in vivo. The PI3K/Akt/mTOR signal pathway was also inactivated by miR-199a-5p agomir in our Ems rat model. Taken together, we concluded that miR-199a-5p targeted ZEB1 to inhibit the EMT of ovarian ectopic endometrial stromal cells via PI3K/Akt/mTOR signal pathway in vitro and in vivo, advancing our understanding of miR-199a-5p as regulators of Ems progression and making contribution to the treatment of Ems.\nSimilar content being viewed by others\nAbbreviations\n- Ems:\n-\nEndometriosis\n- EcSCs:\n-\nEctopic endometrial stromal cells\n- CSCs:\n-\nControl endometrial stromal cells\n- EMT:\n-\nEpithelial-mesenchymal transition\n- VEGF:\n-\nVascular endothelial growth factor\nReferences\nMehedintu C, Plotogea MN, Ionescu S, Antonovici M. Endometriosis still a challenge. J Med Life. 2014;7:349–57.\nGaetje R, Kotzian S, Herrmann G, Baumann R, Starzinski-Powitz A. Invasiveness of endometriotic cells in vitro. Lancet. 1995;346:1463–4.\nFukunaga M. Uterus-like mass in the uterine cervix: superficial cervical endometriosis with florid smooth muscle metaplasia? 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Sci. 27, 110–118 (2020). https://doi.org/10.1007/s43032-019-00016-5\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s43032-019-00016-5","source_license":"CC0","license_restricted":false}