Circ_0115118 regulates endometrial functions through the miR-138-1-3p/WDFY2 axis in patients with PCOS†

Abstract

To investigate the expression profiles of circular RNAs (circRNAs) in the endometria of women with polycystic ovary syndrome (PCOS) and to explore the role of aberrant circ_0115118 expression in endometrial dysfunction in patients with PCOS. CircRNA microarray hybridization and bioinformatic analyses were performed to determine the expression patterns of circRNAs in the endometria of patients with or without PCOS, the expression of target circRNA was evaluated by real-time polymerase chain reaction (PCR). Cell counting kit-8 and Transwell assays were used to detect cellular proliferative, invasive, and migratory capacities. The influence of the circRNA on decidualization was explored by real-time PCR. Animal models were established to investigate the regulatory effect of the circRNA on embryo implantation. Downstream microRNAs and genes were predicted using bioinformatic websites and verified by dual-luciferase reporter assays, real-time PCR, and western blotting. In the endometria of patients with PCOS, there were 113 differentially expressed circRNAs in the secretory phase and 1119 differentially expressed circRNAs in the proliferative phase. The expression of circ_0115118 was significantly higher in endometrial stromal cells during the proliferative phase in patients with PCOS, leading to inhibition of cellular mobilization and embryo implantation. In addition, circ_0115118 exerted effects by sponging miR-138-1-3p, subsequently increasing the expression of WD repeat and FYVE domain-containing protein 2 (WDFY2). Circ_0115118 expression is dysregulated in the endometria of patients with PCOS and adversely affects endometrial function. Our findings reveal that circ_0115118 may be a potential therapeutic target to improve pregnancy outcomes in women with PCOS.

Keywords: circular RNA; endometrium; microRNA; polycystic ovary syndrome; stromal cells.