Hsa_circ_0043533 modulates apoptosis and viability of granulosa cells via miR-409-3p/BCL2 and EMT signalling in PCOS: Providing novel perspective of metformin

Polycystic ovary syndrome (PCOS) represents a significant cause of infertility among women of reproductive age. Studies have established a close association between granulosa cells (GCs) and the abnormal follicle formation and ovulation processes characteristic of PCOS. The interactions among hsa_circ_0043533, miR-409–3p, and BCL2 were verified through luciferase activity assays. In PCOS patients, granulosa cells exhibit notably reduced apoptosis but enhanced growth, leading to their accumulation and the development of polycystic ovaries. The involvement of non-coding RNAs in PCOS has been documented, with elevated levels of hsa_circ_0043533 observed in this condition. A comprehensive series of experiments were conducted to explore the role of hsa_circ_0043533 in PCOS and elucidate its underlying mechanisms. Silencing hsa_circ_0043533 was found to promote apoptosis and hinder the migration, proliferation, and viability of KGN cells. Furthermore, we uncovered the regulatory effects of hsa_circ_0043533 on the miR-409–3p/BCL2 axis and key markers of Epithelial-Mesenchymal Transition (EMT). Additionally, it was observed that metformin modulates the hsa_circ_0043533/miR-409–3p/BCL2 axis. Overall, this study provides novel insights into the molecular mechanisms regulating granulosa cell proliferation and apoptosis in PCOS, further elucidating the molecular pathogenesis of this condition.