Zhou Lifei, Zheng Bo, Luo Yan, Zhang Pingping, Dai Fangfang, Zhang Mingming, Wang Shusong, Li Yali
Department of Reproductive and Genetics, Hebei General Hospital, Shijiazhuang, 050000, Hebei, China.
Xingtai Infertility Specialist Hospital, Xingtai, 054000, Hebei, People's Republic of China.
Reprod Sci. 2025 Aug 25. doi: 10.1007/s43032-025-01932-5.
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.
颗粒细胞的异常发育被广泛认为是导致多囊卵巢综合征(PCOS)的关键因素。然而,这种疾病的确切病因和潜在机制在很大程度上仍然难以捉摸。越来越多的证据表明,微小RNA(miRNA)的失调在PCOS的发病机制中起关键作用。在本研究中,我们系统地研究了miR-30c-5p对人卵丘细胞(CCs)的功能影响。我们的研究结果表明,miR-30c-5p通过靶向沉默信息调节因子1(SIRT1)抑制人颗粒细胞瘤细胞系(KGN)的增殖并诱导其凋亡。值得注意的是,与健康对照组相比,PCOS患者中miR-30c-5p的表达水平显著升高,而SIRT1的表达则明显降低。miR-30c-5p与SIRT1的表达之间存在负相关。机制上,miR-30c-5p的上调导致SIRT1和Bcl-2蛋白的表达降低,同时增强Bax蛋白的表达。此外,我们的数据证实SIRT1是miR-30c-5p的直接靶点。总体而言,这些结果表明,miR-30c-5p通过直接靶向SIRT1促进颗粒细胞凋亡,从而代表了改善PCOS患者颗粒细胞功能障碍的新分子靶点。