Abstract Abnormal development of granulosa cells is widely recognized as a critical factor contributing to polycystic ovary syndrome (PCOS). However, the precise etiology and underlying mechanisms of this disorder remain largely elusive. Accumulating evidence suggests that dysregulation of microRNAs (miRNAs) plays a pivotal role in the pathogenesis of PCOS. In this study, we systematically investigated the functional impact of miR-30c-5p on the human cumulus cells (CCs). Our findings revealed that miR-30c-5p suppresses the proliferation and induces apoptosis in the human granulosa-like tumor cell line (KGN) via targeting SIRT1. Notably, the expression level of miR-30c-5p was significantly elevated in PCOS patients compared to healthy controls, whereas the expression of SIRT1 was markedly reduced. A negative correlation was observed between miR-30c-5p and SIRT1 expression. Mechanistically, upregulation of miR-30c-5p led to decreased expression of SIRT1 and Bcl-2 proteins, while simultaneously enhancing the expression of Bax proteins. Furthermore, our data confirmed that SIRT1 serves as a direct target of miR-30c-5p. Collectively, these results indicate that miR-30c-5p promotes apoptosis of GCs by directly targeting SIRT1, thereby representing a novel molecular target for improving GC dysfunction in PCOS patients.
Zhou et al. (Mon,) studied this question.
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