Han Zhou, Chao Wang, Wentao Wang, Pin Guo, Yifan Xu, Zhenwen Cui, Xiaolu Li, Shifang Li, Yugong Feng, Tao Yu
{"title":"CircGNAQ通过促进血管平滑肌细胞表型转换和凋亡促进颅内动脉瘤形成。","authors":"Han Zhou, Chao Wang, Wentao Wang, Pin Guo, Yifan Xu, Zhenwen Cui, Xiaolu Li, Shifang Li, Yugong Feng, Tao Yu","doi":"10.1177/15230864251380271","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Aims:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Innovation and Conclusion:</i></b> 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. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":6.1000,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CircGNAQ Promotes Intracranial Aneurysm Formation by Facilitating Vascular Smooth Muscle Cell Phenotypic Switching and Apoptosis.\",\"authors\":\"Han Zhou, Chao Wang, Wentao Wang, Pin Guo, Yifan Xu, Zhenwen Cui, Xiaolu Li, Shifang Li, Yugong Feng, Tao Yu\",\"doi\":\"10.1177/15230864251380271\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b><i>Aims:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Innovation and Conclusion:</i></b> 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. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>\",\"PeriodicalId\":8011,\"journal\":{\"name\":\"Antioxidants & redox signaling\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2025-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antioxidants & redox signaling\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1177/15230864251380271\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antioxidants & redox signaling","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1177/15230864251380271","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
CircGNAQ Promotes Intracranial Aneurysm Formation by Facilitating Vascular Smooth Muscle Cell Phenotypic Switching and Apoptosis.
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.
期刊介绍:
Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas.
ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes.
ARS coverage includes:
-ROS/RNS as messengers
-Gaseous signal transducers
-Hypoxia and tissue oxygenation
-microRNA
-Prokaryotic systems
-Lessons from plant biology