The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China.
Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
Biochem Biophys Res Commun. 2020 Apr 16;524(4):791-797. doi: 10.1016/j.bbrc.2020.01.046. Epub 2020 Feb 1.
Increased granulosa cell (GC) proliferation may contribute to abnormal folliculogenesis in patients with polycystic ovary syndrome (PCOS), which affects approximately 10% reproductive aged women. However, the mechanisms underlying increased GC proliferation in PCOS remain incompletely understood. In this study, we identified miR-3940-5p as a hub miRNA in GC from PCOS using weighted gene co-expression network analysis (WGCNA), and real-time polymerase chain reaction (RT-PCR) analysis confirmed that miR-3940-5p was significantly increased in GC from PCOS. Enrichment analysis of predicted target genes of miR-3940-5p indicated potential roles of miR-3940-5p in follicular development and cell proliferation regulation. Consistently, functional study confirmed that miR-3940-5p overexpression promoted granulosa cell proliferation. Integrated analysis of mRNA expression profiling data and predicted target genes of miR-3940-5p identified potassium voltage-gated channel subfamily A member 5 (KCNA5) as a potential target of miR-3940-5p, and was validated by luciferase reporter assay. Finally, functional analysis suggested that miR-3940-5p promoted GC proliferation in a KCNA5 dependent manner. In conclusion, miR-3940-5p was a hub miRNA upregulated in GC from PCOS, and promoted GC proliferation by targeting KCNA5.
在多囊卵巢综合征（PCOS）患者中，颗粒细胞（GC）增殖增加可能导致卵泡发生异常，这影响了大约 10%的育龄妇女。然而，PCOS 中 GC 增殖增加的机制仍不完全清楚。在这项研究中，我们使用加权基因共表达网络分析（WGCNA）鉴定出 miR-3940-5p 是 PCOS 中 GC 的枢纽 miRNA，实时聚合酶链反应（RT-PCR）分析证实 miR-3940-5p 在 PCOS 的 GC 中显著增加。miR-3940-5p 预测靶基因的富集分析表明 miR-3940-5p 在卵泡发育和细胞增殖调节中具有潜在作用。一致地，功能研究证实 miR-3940-5p 过表达促进了颗粒细胞增殖。miR-3940-5p 的 mRNA 表达谱数据和预测靶基因的综合分析鉴定出钾电压门控通道亚家族 A 成员 5（KCNA5）是 miR-3940-5p 的潜在靶标，并通过荧光素酶报告基因实验得到验证。最后，功能分析表明 miR-3940-5p 通过靶向 KCNA5 促进 GC 增殖。总之，miR-3940-5p 是 PCOS 中 GC 上调的枢纽 miRNA，通过靶向 KCNA5 促进 GC 增殖。
