Altered miR-186 and miR-135a contribute to granulosa cell dysfunction by targeting ESR2: A possible role in polycystic ovary syndrome

MicroRNAs (miRNAs) are a group of negative regulators of gene expression that function at the posttranscriptional level. Dysregulation of miRNAs is involved in many pathophysiological processes, including polycystic ovary syndrome (PCOS). In this study, we first detected the expression levels of 6 candidate miRNA in granulosa cells (GCs) from 63 women with PCOS and 20 healthy controls. We found that miR-186 and miR-135a were overexpressed in GCs from PCOS patients. Subsequently, the direct targets of miR-186 and miR-135a were predicted using bioinformatics analysis and verified by luciferase assays and immunoblotting. The present study determined that miR-186 and miR-135a repressed ESR2 expression in GCs, which further inhibited CDKN1A expression, promoted GC proliferation and repressed GC apoptosis. Meanwhile, the levels of miR-186 and miR-135a in GCs were found to positively correlate with serum estradiol levels in patients with PCOS. Furthermore, estradiol treatment directly increased miR-186 and miR-135a levels in KGN and primary GCs, which provides new insight into understanding the pathophysiology of PCOS.