MiR-3940-5p promotes granulosa cell proliferation through targeting KCNA5 in polycystic ovarian syndrome
MiR-3940-5p promotes granulosa cell proliferation through targeting KCNA5 in polycystic ovarian syndrome
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MiR-3940-5p 通过靶向 KCNA5 促进多囊卵巢综合征中的颗粒细胞增殖
DOI：
10.1016/j.bbrc.2020.01.046
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发表时间：
2020-04-16
影响因子：
3.1
通讯作者：
Huang, Hefeng
中科院分区：
文献类型：
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作者：
Gao, Ling;Wu, Dandan;Huang, Hefeng
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生成异常，大约10%的育龄妇女受到影响。然而，PCOS中GC增殖增加的机制尚不完全清楚。在本研究中，我们使用加权基因共表达网络分析（WGCNA）确定miR-3940-5p是PCOS GC中的枢纽miRNA，实时聚合酶链反应（RT-PCR）分析证实，miR-3940-5p在PCOS GC中显著升高。对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控中的潜在作用。与此一致，功能研究证实miR-3940-5p过表达促进颗粒细胞增殖。通过对miR-3940-5p mRNA表达谱数据和预测靶基因的综合分析，确定了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试验进行了验证。最后，功能分析表明miR-3940-5p以KCNA5依赖的方式促进GC增殖。综上所述，miR-3940-5p是PCOS中GC上调的枢纽miRNA，并通过靶向KCNA5促进GC增殖。(C) 2020爱思唯尔公司版权所有。
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. (C) 2020 Elsevier Inc. All rights reserved.