Huang XiaLing, Yu Fen
Department Of gynecology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan City, Hubei Province, China.
Gynecol Endocrinol. 2025 Dec;41(1):2536579. doi: 10.1080/09513590.2025.2536579. Epub 2025 Jul 31.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, yet its underlying mechanisms remain incompletely understood. This study investigated the role of hsa_circ_0020491 in PCOS pathogenesis, focusing on granulosa cells (GCs). Analysis of GCs from PCOS patients and controls revealed significant upregulation of both hsa_circ_0020491 and IGF2BP2, with their expression levels positively correlated. In a dihydrotestosterone (DHT)-treated KGN cell model of PCOS, silencing either circ_0020491 or IGF2BP2 mitigated autophagy dysregulation and mitochondrial dysfunction, evidenced by altered autophagy-related proteins, mitochondrial membrane potential, ATP levels, mtDNA content, and reactive oxygen species. Mechanistically, circ_0020491 binds to and stabilizes IGF2BP2, amplifying its effects. Overexpression of IGF2BP2 counteracted the improvements induced by circ_0020491 knockdown. In vivo, a dehydroepiandrosterone (DHEA)-induced PCOS mouse model confirmed that circ_0020491 suppression attenuated disease progression, improved mitochondrial function, and reduced excessive autophagy. These findings demonstrate that hsa_circ_0020491 exacerbates PCOS by interacting with IGF2BP2 to disrupt autophagy and mitochondrial homeostasis in GCs, offering a potential therapeutic target.
多囊卵巢综合征（PCOS）是一种常见的女性内分泌疾病，但其潜在机制仍未完全明确。本研究聚焦于颗粒细胞（GCs），探讨了hsa_circ_0020491在PCOS发病机制中的作用。对PCOS患者和对照组的GCs分析显示，hsa_circ_0020491和IGF2BP2均显著上调，且它们的表达水平呈正相关。在二氢睾酮（DHT）处理的PCOS KGN细胞模型中，沉默circ_0020491或IGF2BP2可减轻自噬失调和线粒体功能障碍，这可通过自噬相关蛋白、线粒体膜电位、ATP水平、线粒体DNA含量和活性氧的改变得到证明。机制上，circ_0020491与IGF2BP2结合并使其稳定，增强其作用。IGF2BP2的过表达抵消了circ_0020491敲低所诱导的改善作用。在体内，脱氢表雄酮（DHEA）诱导的PCOS小鼠模型证实，circ_0020491的抑制可减缓疾病进展，改善线粒体功能，并减少过度自噬。这些发现表明，hsa_circ_0020491通过与IGF2BP2相互作用破坏GCs中的自噬和线粒体稳态，从而加重PCOS，提供了一个潜在的治疗靶点。
