Metformin enhances the survival ability of ovarian granulosa cells in polycystic ovary syndrome by promoting LINC00548 to suppress androgen receptor/klotho pathway

Abstract Background Metformin (Met) has been reported to play the key role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the precise mechanisms underlying the actions of Met in PCOS remain incompletely understood. This study aimed to confirm the mechanism of Met interacting with a long non‐coding RNA LINC00548 in PCOS. Methods Ovarian granulosa cells (OGCs) were incubated 500 nM dihydrotestosterone (DHT) to construct PCOS in vitro model and then were treated 20 μM Met. A series of cell experiments including Cell Counting Kit‐8, Terminal uridine nucleotide end labeling, and flow cytometry were performed to confirm the changes of OGC survival ability. Quantitative real‐time polymerase chain reaction was conducted to determine the levels of LINC00548, whereas Western blotting was applied to determine the levels of androgen receptor (AR) and klotho. Results Met improved the cell viability and suppressed cell apoptosis in DHT‐treated OGCs. LINC00548 downregulated in DHT‐treated OGCs was upregulated by Met, and its overexpression further enhanced the positive effects of Met on the survival ability of DHT‐treated OGCs. In addition, Met could induce the upregulation of LINC00548 to suppress the activation of AR/klotho pathway in DHT‐treated OGCs. Conclusion Overall, this study discovers that Met enhances the survival ability of OGCs in PCOS by elevating LINC00548 expression to suppress AR/klotho pathway.