lncRNA PVT1/MicroRNA-17-5p/PTEN Axis Regulates Secretion of E2 and P4 Proliferation and Apoptosis of Ovarian Granulosa Cells in PCOS

摘要

Recently, the roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were identified in polycystic ovary syndrome (PCOS). In the present study, we investigated the role of the lncRNA PVT1/miR-17-5p/PTEN axis in PCOS ovarian granulosa cells. Expression of PVT1, miR-17-5p and PTEN in PCOS ovarian granulosa cells and follicular fluid was detected, and homeostatic model assessment of insulin resistance (HOMA-IR) and the levels of fasting plasma glucose (FPG), fasting insulin (FINS), and sex hormones were assessed. Then, the proliferation, apoptosis, and colony formation ability of ovarian granulosa cells were evaluated. The binding relationship between PVT1 and miR-17-5p as well as the target relationship between miR-17-5p and PTEN were determined by bioinformatics analysis, luciferase activity assay, RNA-induced silencing complex assay, and RNA pull-down assay. The levels of sex hormone-binding globulin and follicle-stimulating hormone were abated and the levels of luteinizing hormone, testosterone, FINS, FPG, and HOMA-IR were increased in PCOS serum. PVT1 and PTEN were overexpressed and miR-17-5p was reduced in PCOS ovarian granulosa cells and follicular fluid. Overexpressed miR-17-5p and inhibited PVT1 could decelerate apoptosis while accelerating colony formation ability and proliferation of ovarian granulosa cells in PCOS. Moreover, overexpression of PVT1 and reduced miR-17-5p could reverse these results. There existed target relation among PVT1, miR-17-5p, and PTEN, and PVT1 could inhibit miR-17-5p, thereby elevating PTEN. Our study suggests that inhibited PVT1 and overexpressed miR-17-5p result in downregulation of PTEN and promotion of cell proliferation, as well as inhibition of apoptosis of ovarian granulosa cells in PCOS.