Inhibition of microRNA-19b promotes ovarian granulosa cell proliferation by targeting IGF-1 in polycystic ovary syndrome.

Abstract

The purpose of the present study was to investigate the functional role of microRNA (miR)-19b in polycystic ovary syndrome (PCOS) and try to elucidate its underlying mechanisms. Expression of miR-19b and insulin-like growth factor 1 (IGF-1) was examined in ovarian cortexes [(from 18 women with PCOS and 10 who did not have PCOS (non-PCOS)] and KGN cells. Cell proliferation assays (cell viability and colony formation assay) were performed following overexpression or inhibition of miR-19b and IGF-1 or following insulin treatment in KGN cells. Expression levels of the cell cycle-associated protein cyclin D1 and cyclin-dependent kinase (CDK) 1 were analyzed following overexpression or inhibition of miR-19b and IGF-1. Potential miR-19b targets were identified by bioinformatics. Luciferase assay, reverse transcription-quantitative polymerase chain reaction and western blotting were performed to determine whether IGF-1 was a target of miR-19b. miR-19b expression was significantly decreased in the PCOS ovarian cortex and KGN cells and its identified target, IGF-1, was upregulated. miR-19b overexpression inhibited cell proliferation at G2/M phrase. Overexpression of IGF-1 promoted cell viability and colony formation ability in KGN cells. The expression of cyclin D1 and CDK1 was statistically increased by inhibition of miR-19b and overexpression of IGF-1. High concentrations of insulin decreased levels of miR-19b, stimulated KGN cell proliferation, and elevated IGF-1 levels. Inhibition of miR-19b promoted ovarian granulosa cell proliferation by targeting IGF-1 in PCOS. Insulin decreased the expression levels of miR-19b and stimulated cell proliferation. The present study suggested that overexpression of miR-19b may be a potential therapeutic approach for PCOS.