Downregulation of FOXO1 in PCOS Granulosa Cells: A Direct Target of microRNA-183.

Abstract

The purpose of this study is to investigate whether microRNA (miR-183) and forkhead box O1 (FOXO1) are abnormally expressed in polycystic ovary syndrome (PCOS) granulosa cells (GCs) and further explore its underlying molecular mechanisms. The expressions of miR-183 and FOXO1 in GCs isolated from 55 PCOS and 60 control patients were determined by quantitative reverse transcription-polymerase chain reaction (q-PCR) and western blot respectively. Granulosa-like tumor cell line (KGN) cells were used to alter the levels of miR-183 and FOXO1 by transfection. The target genes of miR-183 were first predicted by bioinformatics analysis and then verified by q-PCR, western blot and luciferase reporter assay. KGN cells were treated by insulin to further verify the relationship between miR-183 and FOXO1. The results demonstrated that the expression of miR-183 was significantly increased in PCOS patients, while FOXO1 was decreased. In addition, FOXO1 was a direct target of miR-183, which was negative with homeostasis model assessment for insulin resistance (HOMA-IR). Moreover, insulin treatment in KGN cells induced upregulation of miR-183 and decreased FOXO1. It could be speculated that insulin-mediated miR-183 targets FOXO1 to regulate the pathogenesis of PCOS, which might provide a new idea for investigating the functional role of miR-183 in PCOS GCs.