miR-202-3p overexpression attenuates endometriosis-like lesions by modulating YAP-dependent transcription of S100A6 in murine models

Recent evidence has suggested the important implications of microRNAs (miRNAs) in the processes of proliferation and tissue remodeling in endometriosis (EMS). We therefore aim to determine the role of miR-202-3p in the pathophysiology of EMS and its underlying mechanisms. Experimental endometriosis was induced in ovariectomized mice implanted with a slow-release 17-β estradiol capsule. Eutopic endometrial stromal cells (euESCs) were isolated and assayed for proliferative, invasive and apoptotic properties by EdU staining, Transwell assays, and flow cytometry. The invasive and apoptotic features in the endometrium of mice with EMS in vivo were evaluated by using immunohistochemical staining and TUNEL assays. miR-202-3p was observed to be downregulated in the endometrial tissues of EMS patients. MiR-202-3p was also found to target YAP1 which resulted in reduced euESC proliferation and invasion and increased apoptosis. YAP1 was able to phosphorylated STAT3 which consequently upregulated S100A6 to promote the proliferative and invasive abilities of euESCs. MiR-202-3p was thereby proposed to act as an inhibitor of proliferation and tissue damage in the in vivo setting of EMS, its effects however, were able to be counteracted byS100A6, which reversed the effects of miR-202-3p on tissue injury and cell proliferation. Our data together evidenced that miR-202-3p targeted YAP1 to reduce STAT3-mediated S100A6 whereby preventing the progression of EMS.