The UCA1 and microRNA-18a signaling pathway mediates the irisin-lowering effect of metformin in the management of polycystic ovary syndrome.

Abstract

IntroductionThe present study aimed to clarify the underlying mechanism of metformin (met) in the management of polycystic ovary syndrome (PCOS) and to explore the role of the UCA1/microRNA-18a signaling pathway in the control of PCOS.Material and methodsReal-time PCR was performed to compare the levels of irisin, blood glucose, UCA1 and miR-18a among PCOS, PCOS + Met, and control groups using area under curve (AUC) values. In-silicon analysis and luciferase assay were performed to explore the regulatory relationship among UCA1, miR-18a and irisin. Real-time PCR and Western blot analysis were carried out to detect the effect of met on the expression of UCA1, miR-18a and irisin.ResultsAUC of UCA1 was the highest while AUC of irisin was the lowest. Also, irisin and UCA1 levels in the PCOS group were much higher than those in the PCOS + Met group, while miR-18a level in the PCOS group was much lower than in the PCOS + Met group. Through the luciferase assay, miR-18a was proved to directly bind to the irisin 3’UTR. Additionally, irisin was identified to be a target gene of miR-18a. Finally, treatment with met at an increasing concentration reduced the level of UCA1 and irisin but increased the level of miR-18a in a dose-dependent manner.ConclusionsIn the management of PCOS, the irisin-lowering effect of met is regulated by the UCA1/miR-18a/RhoB signaling pathway.