Abstract:To investigate the expression of MicroRNA-215-5p (miR-215-5p) in polycystic ovary syndrome (PCOS) rats and its influence on ovarian granulosa cell (GC) apoptosis, and analyze the underlying mechanism. Methods Dehydroepiandrosterone (DHEA) was used to establish a PCOS rat model, and primary PCOS rat ovarian GCs were isolated and cultured. They were grouped into control group, sh-NC group, sh-YY1 group, sh-YY1+LY2109761 group, miR-NC group, miR-215-5p mimic group, miR-215-5p mimic+pc=NC group, and miR-215-5p mimic+pc-YY1 group. The GC apoptosis in PCOS rat ovarian tissue was detected by TUNEL method; the mRNA expression of miR-215-5p and Yin-Yang-1 (YY1) in ovarian tissue/GC was measured by real-time quantitative PCR (RT-qPCR); cell proliferation ability was detected by CCK-8 method and plate colony formation assay; cell apoptosis rate was measured by flow cytometry; the protein expression of YY1, transforming growth factor-β1 (TGF-β1) and Smad4 in ovarian tissue/GC of PCOS rats was detected by Western blot. Results The expression of miR-215-5p was low in the ovarian tissue of PCOS rats, and the mRNA and protein levels of YY1 were significantly increased in the ovarian tissue of PCOS rats (P<0.05). Knockdown of YY1 or up-regulation of miR-215-5p was able to significantly enhance the proliferation of ovarian GCs in PCOS rats, inhibit GC apoptosis, and increase the levels of TGF-β1 and Smad4 proteins (all P<0.05). TGF-β/Smad4 signaling pathway inhibitor LY2109761 was able to significantly attenuate the inhibitory effect of knockdown of YY1 on ovarian GC apoptosis (P<0.05); on the basis of overexpression of miR-215-5p, up-regulation of YY1 was able to inhibit the activation of TGF-β1/Smad signaling pathway, and significantly attenuate the inhibitory effect of miR-215-5p mimic on ovarian GC apoptosis in PCOS rats (P<0.05). Conclusion MiR-215-5p is lowly expressed in PCOS. Overexpression of miR-215-5p may promote the proliferation of ovarian GC and inhibit apoptosis in PCOS rats by downregulating YY1 and activating the TGF-β1/Smad signaling pathway