Liping Wang, Chenyue Tao, Shuai Chen, Liu Gui, Yitong Zhang, Min Jiang, Dongjie Zhou, Luojing Zhou
Department of Biobank, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, China.
School of Public Health, Yangzhou University, Yangzhou, Jiangsu, China.
Gynecol Endocrinol. 2025 Dec;41(1):2526559. doi: 10.1080/09513590.2025.2526559. Epub 2025 Jul 2.
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.
多囊卵巢综合征（PCOS）是一种常见的生殖和代谢紊乱疾病，可导致育龄女性不孕。已知环状RNA参与PCOS的发生发展，但其调控机制尚不清楚。本研究探讨了circ_BMPR2在PCOS中的作用，以推进早期诊断和治疗。研究发现PCOS患者卵巢颗粒细胞中circ_BMPR2表达升高。敲低circ_BMPR2可抑制KGN细胞增殖并促进其凋亡。机制上，我们证实circ_BMPR2作为海绵结合miR-619-5p，miR-619-5p可特异性靶向Rab43基因。PCOS组织中Rab43表达上调，沉默circ_BMPR2可降低Rab43水平，而miR-619-5p抑制剂可挽救这一作用。进一步实验证实，Rab43过表达可逆转circ_BMPR2敲低对KGN细胞增殖和凋亡的影响。因此，我们的研究结果表明，circ_BMPR2通过调节miR-619-5p/Rab43轴调控颗粒细胞的生长和细胞周期进程，在PCOS进程中起关键作用。这表明circ_BMPR2可能是PCOS早期诊断的潜在生物标志物。通过了解其分子机制，我们可为治疗这种复杂疾病的更有效干预措施铺平道路。
