MiR-199a-5p Targets ZEB1 to Inhibit the Epithelial-Mesenchymal Transition of Ovarian Ectopic Endometrial Stromal Cells Via PI3K/Akt/mTOR Signal Pathway In Vitro and In Vivo.

Endometriosis (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.