Liu Yu-Dong, Li Ying, Feng Shu-Xian, Ye De-Sheng, Chen Xin, Zhou Xing-Yu, Chen Shi-Ling
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
Endocrinology. 2017 Nov 1;158(11):3890-3899. doi: 10.1210/en.2017-00605.
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.
多囊卵巢综合征（PCOS）是育龄期女性无排卵性不孕最常见的原因，其病因仍知之甚少。长链非编码RNA（lncRNA）活性的改变与人类疾病和发育有关。然而，lncRNA在生殖医学中的作用尚不清楚。我们使用人颗粒细胞（GCs）和KGN细胞系，研究lncRNA在PCOS发病机制中的潜在作用。我们使用微阵列比较了7例PCOS患者和7例匹配对照女性的GCs中lncRNA表达谱。2014年至2016年期间，从中国广州的不孕女性中收集GC样本。采用定量实时聚合酶链反应检测53例PCOS患者和50例对照者GCs中lncRNA HCG26的水平。在KGN细胞中用锁核酸GapmeRs敲低HCG26，以研究其在细胞增殖、芳香化酶和促卵泡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（变化大于或等于两倍；P<0.05）。PCOS患者中HCG26水平上调，并与窦卵泡计数相关。KGN细胞中HCG26敲低抑制细胞增殖和细胞周期进程，并增加芳香化酶基因表达和雌二醇产生。我们的研究报告了PCOS患者和健康女性GCs中的lncRNA谱，并表明lncRNA失调可能在GC增殖和类固醇生成中起重要作用，为PCOS的发病机制提供了见解。
