{"title":"环状RNA circLIMK1-005通过与RPA1蛋白相互作用激活CDK4信号传导,促进肺腺癌的进展。","authors":"Xia Yang, Lu Liu, Zhongjian Yu, Yuanlin Chen, Shiting Xu, Meiyuan Liu, Meng Wang, Huili Guo, Zhiwu Zhang, Bingjie Shan, Silin Cai, Mengting Pan, Jiangyu Zhang, Fengpin Wang, Yanfang Zheng","doi":"10.1038/s41420-025-02565-y","DOIUrl":null,"url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is the leading cause of cancer death worldwide. Circular RNAs (circRNAs) have emerged as potential key players in the onset and progression of various cancers. However, the specific roles and mechanisms of circRNAs in LUAD remain largely unexplored. Here, we aimed to elucidate the role of a particular novel circRNA, circLIMK1-005 (hsa_circ_0002690), in the pathogenesis of LUAD. Our study revealed that circLIMK1-005 was upregulated in LUAD and correlated with poor patient prognosis. Functionally, circLIMK1-005 significantly promoted LUAD cell proliferation and metastasis. Mechanistically, circLIMK1-005 elevated the expression of Cyclin D1 and CDK4 proteins, thereby activating CDK4 signaling. We further demonstrated that circLIMK1-005 promoted LUAD progression by binding with RPA1 protein and activating the CDK4 pathway. In vivo experiments corroborated these findings, confirming that the circLIMK1-005/RPA1/CDK4 axis contributed to LUAD progression and was associated with poor clinical outcomes. Our study revealed a novel mechanism of the circLIMK1-005/RPA1/CDK4 axis in LUAD progression, and highlighted that targeting circLIMK1-005 could represent a potential therapeutic strategy for patients with LUAD. Schematic diagram of hypothesis involved in the circLIMK1-005/RPA1/CDK4 axis in LUAD progression. Figure was created with BioGDP.com.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"297"},"PeriodicalIF":7.0000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218172/pdf/","citationCount":"0","resultStr":"{\"title\":\"Circular RNA circLIMK1-005 promotes the progression of lung adenocarcinoma by interacting with RPA1 protein to activate CDK4 signaling.\",\"authors\":\"Xia Yang, Lu Liu, Zhongjian Yu, Yuanlin Chen, Shiting Xu, Meiyuan Liu, Meng Wang, Huili Guo, Zhiwu Zhang, Bingjie Shan, Silin Cai, Mengting Pan, Jiangyu Zhang, Fengpin Wang, Yanfang Zheng\",\"doi\":\"10.1038/s41420-025-02565-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Lung adenocarcinoma (LUAD) is the leading cause of cancer death worldwide. Circular RNAs (circRNAs) have emerged as potential key players in the onset and progression of various cancers. However, the specific roles and mechanisms of circRNAs in LUAD remain largely unexplored. Here, we aimed to elucidate the role of a particular novel circRNA, circLIMK1-005 (hsa_circ_0002690), in the pathogenesis of LUAD. Our study revealed that circLIMK1-005 was upregulated in LUAD and correlated with poor patient prognosis. Functionally, circLIMK1-005 significantly promoted LUAD cell proliferation and metastasis. Mechanistically, circLIMK1-005 elevated the expression of Cyclin D1 and CDK4 proteins, thereby activating CDK4 signaling. We further demonstrated that circLIMK1-005 promoted LUAD progression by binding with RPA1 protein and activating the CDK4 pathway. In vivo experiments corroborated these findings, confirming that the circLIMK1-005/RPA1/CDK4 axis contributed to LUAD progression and was associated with poor clinical outcomes. Our study revealed a novel mechanism of the circLIMK1-005/RPA1/CDK4 axis in LUAD progression, and highlighted that targeting circLIMK1-005 could represent a potential therapeutic strategy for patients with LUAD. Schematic diagram of hypothesis involved in the circLIMK1-005/RPA1/CDK4 axis in LUAD progression. Figure was created with BioGDP.com.</p>\",\"PeriodicalId\":9735,\"journal\":{\"name\":\"Cell Death Discovery\",\"volume\":\"11 1\",\"pages\":\"297\"},\"PeriodicalIF\":7.0000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218172/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Death Discovery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41420-025-02565-y\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02565-y","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Circular RNA circLIMK1-005 promotes the progression of lung adenocarcinoma by interacting with RPA1 protein to activate CDK4 signaling.
Lung adenocarcinoma (LUAD) is the leading cause of cancer death worldwide. Circular RNAs (circRNAs) have emerged as potential key players in the onset and progression of various cancers. However, the specific roles and mechanisms of circRNAs in LUAD remain largely unexplored. Here, we aimed to elucidate the role of a particular novel circRNA, circLIMK1-005 (hsa_circ_0002690), in the pathogenesis of LUAD. Our study revealed that circLIMK1-005 was upregulated in LUAD and correlated with poor patient prognosis. Functionally, circLIMK1-005 significantly promoted LUAD cell proliferation and metastasis. Mechanistically, circLIMK1-005 elevated the expression of Cyclin D1 and CDK4 proteins, thereby activating CDK4 signaling. We further demonstrated that circLIMK1-005 promoted LUAD progression by binding with RPA1 protein and activating the CDK4 pathway. In vivo experiments corroborated these findings, confirming that the circLIMK1-005/RPA1/CDK4 axis contributed to LUAD progression and was associated with poor clinical outcomes. Our study revealed a novel mechanism of the circLIMK1-005/RPA1/CDK4 axis in LUAD progression, and highlighted that targeting circLIMK1-005 could represent a potential therapeutic strategy for patients with LUAD. Schematic diagram of hypothesis involved in the circLIMK1-005/RPA1/CDK4 axis in LUAD progression. Figure was created with BioGDP.com.
期刊介绍:
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.