Mechanistic Study of MiR-30c-5p Regulation of SIRT Expression in Polycystic Ovary Syndrome

TL;DR

This study explores how miR-30c-5p affects granulosa cell function in polycystic ovary syndrome by targeting SIRT1.

Contribution

The study identifies miR-30c-5p as a novel regulator of SIRT1 in PCOS granulosa cells.

Findings

miR-30c-5p suppresses proliferation and induces apoptosis in granulosa-like tumor cells.

miR-30c-5p expression is elevated in PCOS patients, while SIRT1 is reduced.

SIRT1 is confirmed as a direct target of miR-30c-5p, linking it to granulosa cell dysfunction in PCOS.

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.

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