Involvement of ferroptosis in the granulosa cells proliferation of PCOS through the circRHBG/miR-515/SLC7A11 axis

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disease among women, but its etiology remains unknown. In recent years, many circular RNAs (circRNAs) have been confirmed to be related to the development of PCOS. The role and mechanism of circRNA in the development of PCOS need to be further explored. Methods: In the present study, we used the circRNA chip to detect the difference in the expression of circRNA in the granulosa cells of PCOS patients and controls. Five upregulated circRNAs were then selected for quantitative reverse transcription polymerase chain reaction (qRT-PCR) verification, and circRHBG was found to be upregulated in PCOS. Subsequently, Cell Counting Kit-8 assay and EdU assay were used to observe the effect of circRHBG on the proliferation of KGN and SVOG cells. Furthermore, the pairwise binding relationship between circRHBG/miR515-5 and miR515-5p/SLC7A11 was verified by luciferase reporter assay. The interaction between circRHBG and SLC7A11 was detected with qRT-PCR and Western blot. Results: CircRNA high-throughput chips and qRT-PCR verified that circRHBG was significantly upregulated in granular cells of PCOS patients. Knockdown of circRHBG inhibits KGN and SVOG cell proliferation. Luciferase reporter assays and Ago2-RIP detection showed that circRHBG competes with SLC7A11 to bind to miR-515-5p. Subsequent experiments verified knockdown of circRHBG promotes ferroptosis in PCOS. Conclusions: circRHBG inhibits ferroptosis in PCOS cells through the circRHBG/miR-515-5p/ SLC7A11 axis in PCOS, which may provide new diagnostic molecular markers and therapeutic targets for PCOS.