Downregulating lncRNA NEAT1 induces proliferation and represses apoptosis of ovarian granulosa cells in polycystic ovary syndrome via microRNA-381/IGF1 axis

Journal of Biomedical Science

Xia Li¹  Yaling Xiao²  Xue Wang²  Qi Yu²  Jingran Zhen²  Zhengyi Sun²  Jiangli Li³ 

[1] Community Health Service Center, Beijing Forestry University, 100053, Beijing, China;Department of Gynecological Endocrinology and Reproduction Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 41 Damucang Hutong, Xicheng, Beijing, China;Department of Obstetrics and Gynecology, Zhongguancun Hospital, 100080, Beijing, China;

关键词: Polycystic ovary syndrome;    Long non-coding RNA nuclear-enriched abundant transcript 1;    MicroRNA-381;    Insulin-like growth factor 1;    Ovarian granulosa cells;    Apoptosis;    Proliferation;   

DOI  :  10.1186/s12929-021-00749-z

来源: Springer

【 摘 要 】

ObjectiveResearchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS.MethodsPCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro.ResultsNEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis.ConclusionInterference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS.

【 授权许可】

CC BY