CircGNAQ Promotes Intracranial Aneurysm Formation by Facilitating Vascular Smooth Muscle Cell Phenotypic Switching and Apoptosis

作者：Han Zhou, Han Zhou, Chao Wang, Chao Wang, Wentao Wang, Wentao Wang, Guo Pin, Yifan Xu, Zhenwen Cui, Xiaolu Li, Shifang Li, Yugong Feng, Yugong Feng, Tao Yu, Tao Yu · 发表于：Antioxidants and Redox Signaling · 年份：2025 · DOI：10.1177/15230864251380271 · 被引用次数：6 · 研究领域：Circular RNAs in diseases、Axon Guidance and Neuronal Signaling、Cancer Mechanisms and Therapy

Aims: Intracranial aneurysm (IA) is a critical cerebrovascular disorder strongly linked to phenotypic switching and apoptosis of vascular smooth muscle cells (VSMCs). This study aimed to investigate the role of circGNAQ in IA development and elucidate its underlying molecular mechanisms. Results: Reverse transcription-quantitative polymerase chain reaction and fluorescence in situ hybridization revealed significant upregulation of circGNAQ in IA tissues, predominantly localized within VSMCs. In vitro, circGNAQ knockdown attenuated hydrogen peroxide-induced VSMC phenotypic switching and apoptosis, whereas circGNAQ overexpression aggravated these pathological processes. RNA pull-down and mass spectrometry demonstrated that circGNAQ specifically binds to serine/arginine-rich splicing factor 1 (SRSF1), promoting its ubiquitination and degradation, thereby destabilizing SRSF1. Cotransfection assays confirmed that SRSF1 functions as a downstream mediator of circGNAQ in regulating VSMC phenotypic switching and apoptosis. In vivo, circGNAQ knockdown significantly suppressed IA formation in a murine model by inhibiting VSMC phenotypic switching and apoptosis. Innovation and Conclusion: This study identifies circGNAQ as a novel regulator of VSMC phenotypic switching and apoptosis through targeting SRSF1. The findings highlight circGNAQ as a potential therapeutic target for preventing and treating IA. Antioxid. Redox Signal. 00, 000–000.