Hsa_circ_0043532 contributes to PCOS through upregulation of CYP19A1 by acting as a ceRNA for hsa-miR-1270

Abstract

Polycystic ovarian syndrome (PCOS) accounts for about 75% of anovulatory infertility. The cause of PCOS is not clear. CircRNAs acting as miRNA sponges mediate the post-transcriptional regulation of multiple genes. CYP19A1 is a limiting enzyme in the ovarian steroidogenesis pathway. However, the mechanism of circRNAs regulating granulosa cell (GC) estradiol secretion in PCOS remains to be elucidated. Bioinformatics was used to predict the potential target miRNAs of circ_0043532 and target genes of miR-1270. Target miRNAs and mRNA expression were verified by qRT-PCR in GCs from 45 women with PCOS and 65 non-PCOS. Western blot, ELISA and dual-luciferase reporter assays were applied to confirm the substrate of miR-1270. Circ_0043532 and CYP19A1 were significant up-regulation in GCs from patients with PCOS. The predicted target miRNAs of circ_0053432, miR-1270, miR-576-5p, miR-421 and miR-142-5p, were notably decreased in GCs from patients with PCOS. Mechanistic experiments showed that circ_0043532 specifically binds to miR-1270. MiR-1270 was negatively regulated by circ_0043532. Concomitantly, miR-1270 inhibited CYP19A1 expression and estradiol production, which could be reversed by circ_0043532 over-expression. We identified that circ_0043532/miR-1270/CYP19A1 axis contributes to the aberrant steroidogenesis of GCs from patients with PCOS. This study broadens the spectrum of pathogenic factors of PCOS, and circ_0043532 might be a potential therapeutic target for PCOS.