microRNA-103 Contributes to Progression of Polycystic Ovary Syndrome Through Modulating the IRS1/PI3K/AKT Signal Axis

Abstract

Background: Polycystic ovary syndrome (PCOS) is a frequent gynecological endocrine disorder, and the majority of PCOS patients experience different degrees of insulin resistance (IR). Nevertheless, the functions of microRNAs (miRNAs) in IR of PCOS remain unclear. In this study, we desired to elucidate the mechanisms of miR-103 in IR of PCOS.

Methods: The ovarian pathological morphology of established PCOS rats was detected by HE staining. Following miR-103 expression determination in the ovarian tissues of PCOS rats, the relationship between its expression and IR was studied. A PCOS/IR cell model was established, and the effect of miR-103 on granulosa cells was determined by CCK-8 assay and flow cytometry. Through online website prediction and consulting related literatures, the target gene of miR-103 and the pathway regulated by the target genes were discovered, which was verified by further experiments.

Results: PCOS rats showed polycystic changes in the ovary and a decrease in granulosa cells, and these symptoms were more pronounced in rats showed IR. miR-103 expressed highly in PCOS and was positively related to IR. miR-103 inhibitor led to improved PCOS-related symptoms. In addition, miR-103 directly targeted IRS1, which was poorly expressed in PCOS, and IRS1 silencing promoted PCOS development. Furthermore, miR-103 regulated the PI3K/AKT pathway by targeting IRS1, and PI3K/AKT pathway suppression reduced the therapeutic effect of miR-103 inhibitor.

Conclusion: This study indicates that miR-103 disrupts the PI3K/AKT pathway activation by targeting IRS1, thereby aggravating PCOS development. miR-103 inhibition may be a promising molecular target for treatment of PCOS.

Keywords: IRS1; Insulin resistance; PI3K/AKT pathway; Polycystic ovary syndrome; microRNA-103.