Long Noncoding RNAs: Potential Regulators Involved in the Pathogenesis of Polycystic Ovary Syndrome
Long Noncoding RNAs: Potential Regulators Involved in the Pathogenesis of Polycystic Ovary Syndrome
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长非编码 RNA：参与多囊卵巢综合征发病机制的潜在调节因子
DOI：
10.1210/en.2017-00605
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发表时间：
2017-11-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Shi-ling
中科院分区：
文献类型：
--
作者：
Liu, Yu-dong;Li, Ying;Chen, Shi-ling
多囊卵巢综合征(PCOS)是育龄妇女无排卵性不孕最常见的原因，其病因目前尚不清楚。长非编码RNA(LncRNAs)的活性改变与人类疾病和发育有关。然而，lncRNAs在生殖医学中的作用尚不清楚。我们利用人颗粒细胞(GCs)和KGN细胞系研究了lncRNAs在PCOS发病机制中的潜在作用。我们使用微阵列比较了七名多囊卵巢综合征患者和七名匹配的女性GC中的lncRNA表达谱。GC样本是在2014年至2016年期间从广州不孕妇女中国身上采集的。采用实时定量聚合酶链式反应检测53例PCOS患者和50例正常对照GCs中hcG26的表达水平。用锁定核酸GapmeRs敲除KGN细胞中的HCG26，以检测其在细胞增殖、芳香酶和卵泡刺激素受体基因表达以及雌二醇产生中的作用。与对照组相比，PCOS GCs中共有862个lncRNA转录本和998个信使RNA转录本差异表达(大于或等于2倍变化；P<；0.05)。PCOS患者血清HCG26水平升高，并与有腔卵泡计数相关。KGN细胞中HCG26基因的敲除抑制了细胞的增殖和细胞周期进程，增加了芳香酶基因的表达和雌二醇的产生。我们的研究报告了PCOS患者和健康女性GCs中的lncRNA谱，提示调控异常的lncRNAs可能在GC的增殖和类固醇生成中发挥重要作用，为PCOS的发病机制提供了新的见解。
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age, and its etiology remains poorly understood. Altered activities of long noncoding RNAs (lncRNAs) have been associated with human diseases and development. However, the roles of lncRNAs are unknown in reproductive medicine. We investigated the potential role of lncRNAs in the pathogenesis of PCOS, using human granulosa cells (GCs) and the KGN cell line. We used microarrays to compare lncRNA expression profiles in GCs from seven patients with PCOS and seven matched women. GC samples were collected during 2014 to 2016 from infertile women in Guangzhou, China. Quantitative real-time polymerase chain reaction was used to measure levels of the lncRNA HCG26 in GCs from 53 patients with PCOS and 50 controls. HCG26 was knocked down with locked nucleic acid GapmeRs in KGN cells to examine its role in cell proliferation, aromatase and follicle-stimulating hormone receptor gene expression, and estradiol production. A total of 862 lncRNA transcripts and 998 messenger RNA transcripts were differentially expressed (greater than or equal to twofold change; P < 0.05) in PCOS GCs compared with those of controls. HCG26 levels were upregulated in patients with PCOS and were associated with antral follicle count. HCG26 knockdown in KGN cells inhibited cell proliferation and cell-cycle progression and increased aromatase gene expression and estradiol production. Our study reports the lncRNA profiles in GCs from patients who have PCOS and those from healthy women and suggests that dysregulated lncRNAs may play vital roles in GC proliferation and steroidogenesis, providing insights into the pathogenesis of PCOS.