Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease that affects women of reproductive age. It is also a significant cause of infertility. Circular RNAs have been found to have a crucial role in the development and progression of reproductive system diseases. In this study, we focused on circ_BECN1 and aimed to investigate its role and mechanism in PCOS, providing a foundation for early diagnosis and treatment of this condition. Our findings revealed an upregulation of circ_BECN1 expression in the ovarian granulosa cells (GCs) of PCOS patients. Additionally, the silencing of circ_BECN1 resulted in inhibited proliferation and enhanced apoptosis of the human ovarian granulosa-like tumor cell line (KGN), therefore implicating circ_BECN1 in the cell cycle process. Through a dual-luciferase reporting assay, we determined that circ_BECN1 acts as a sponge for miR-619-5p and that Rab5b is the target gene of miR-619-5p. Moreover, the expression of Rab5b was found to be upregulated in the ovarian tissue of PCOS patients. Knocking down circ_BECN1 resulted in decreased Rab5b expression, which was then restored by using a miR-619-5p inhibitor. Additionally, rescue experiments demonstrated that overexpressing Rab5b reversed the effects of circ_BECN1 knockdown on cell proliferation and apoptosis in KGN cells. In summary, our findings indicate that circ_BECN1 is upregulated in PCOS GCs and promotes cell growth and cell cycle progression, and reduces cell apoptosis by modulating the miR-619-5p/Rab5b axis. Therefore, circ_BECN1 may serve as a potential therapeutic target for PCOS treatment.
Wang Liping,Tao Chenyue,Chen Shuai,Gui Liu,Zhang Yitong,Jiang Min,Zhou Dongjie,Zhou Luojing
Polycystic Ovary Syndrome (PCOS) is a common reproductive and metabolic disorder causing infertility in women of childbearing age.Circular RNAs are known to be involved in PCOS development, but their regulatory mechanisms remain unclear. This study explored the role of circ_BMPR2 in PCOS to advance early diagnosis and treatment.It found elevated circ_BMPR2 expression in ovarian granulosa cells of PCOS patients. Knocking down of circ_BMPR2 inhibited proliferation and promoted apoptosis in KGN cell. Mechanistically, we confirmed that circ_BMPR2 acts as a sponge to bind miR-619-5p, which could specifically target Rab43 gene.PCOS tissues showed upregulated Rab43, and silencing circ_BMPR2 reduced Rab43 levels, rescued by a miR-619-5p inhibitor. Further experiments confirmed that overexpression of Rab43 reversed the effects of circ_BMPR2 knockdown on cell proliferation and apoptosis in KGN cells. Thus,our findings implicate circ_BMPR2 acts as a key player in PCOS process, by modulating growth and cell cycle progression of GCs through regulating the miR-619-5p/Rab43 axis. This suggests that circ_BMPR2 could be a prospective biomarker for the early diagnosis of PCOS. By understanding its molecular mechanisms, we can pave the way for more effective interventions to treat this complex disease.
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