Long Noncoding RNAs: Potential Regulators Involved in the Pathogenesis of Polycystic Ovary Syndrome

• Published in: Endocrinology (Philadelphia) 2017-11, Vol.158 (11), p.3890-3899
• Main Authors: Liu, Yu-dong, Li, Ying, Feng, Shu-xian, Ye, De-sheng, Chen, Xin, Zhou, Xing-yu, Chen, Shi-ling
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Adult; Aromatase; Case-Control Studies; Cell growth; Cell Line; Cell proliferation; DNA microarrays; Endocrinology; Etiology; Female; Follicle-stimulating hormone; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genetic Predisposition to Disease; Granulosa cells; Humans; Infertility; Infertility, Female - genetics; Microarray Analysis; mRNA; Non-coding RNA; Nucleic acids; Ovaries; Pathogenesis; Patients; Polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Polymerase chain reaction; Real time; Regulators; Ribonucleic acid; RNA; RNA, Long Noncoding - physiology; Sex hormones; Steroidogenesis; Young Adult
• ISSN: 0013-7227; 1945-7170
• 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.A large number of lncRNAs were dysregulated in PCOS granulosa cells. lincRNA-HCG26 may affect cell proliferation and steroidogenesis in granulosa cells, contributing to the pathogenesis of PCOS.