Long Non-Coding RNA LINC-01572:28 Inhibits Granulosa Cell Growth Via a Decrease in p27 (Kip1) Degradation in Patients with Polycystic Ovary Syndrome

Abstract

Disordered folliculogenesis is a key feature of polycystic ovary syndrome (PCOS), but the underlying molecular mechanism remains unclear. Long non-coding RNA (lncRNA) expression in luteinized granulosa cells (hLGCs) derived from women with and without PCOS were analyzed using microarray and qRT-PCR. Immortalized human granulosa cell lines were cultured for proliferation assays after transfection with the LINC-01572:28 over-expression vector in the presence or absence of p27 siRNA. Protein expression analysis, rescue assays, and RNA immunoprecipitation (RIP) were used to confirm the LINC-01572:28 substrate. LINC-01572:28 and p27 protein were elevated whereas proliferating cell nuclear antigen protein was decreased in the hLGCs of women with PCOS. LINC-01572:28 expression was positively correlated with basal testosterone levels. Over-expression of LINC-01572:28 inhibited cell proliferation and impeded G1/S transition, which were partially reversed by siRNA-mediated p27 knockdown. Our findings, therefore, suggest that LINC-01572:28 suppresses cell proliferation and cell cycle progression by reducing the degradation of p27 protein via SKP2 binding. Funding: This research was supported by grants from the National Key Research and Development Program of China(2017YFC1001002, the National Natural Science Foundation (81490743, 81671413 and 81671414), National Institutes of Health (1R01HD085527), Shanghai Municipal Education Commission--Gaofeng Clinical Medicine (20152510) and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics (17DZ2271100). Declaration of Interests: Authors have no conflicts of interest to declare. Ethical Approval Statement: The study was approved by the ART Ethnics committee of Ren Ji hospital, school of medicine, shanghai Jiao Tong university (number: 2017041411), and informed consent was obtained from all participants.