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

Abstract

Introduction: The 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 methods: Real-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. Results: AUC 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. Conclusions: In the management of PCOS, the irisin-lowering effect of met is regulated by the UCA1/miR-18a/RhoB signaling pathway.