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miR-3940-5p 通过靶向 KCNA5 促进多囊卵巢综合征颗粒细胞增殖。

MiR-3940-5p promotes granulosa cell proliferation through targeting KCNA5 in polycystic ovarian syndrome.

机构信息

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.

出版信息

Biochem Biophys Res Commun. 2020 Apr 16;524(4):791-797. doi: 10.1016/j.bbrc.2020.01.046. Epub 2020 Feb 1.

Abstract

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.

摘要

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。

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