{"title":"NR2F6通过E2F2-PARP1通路调控胶质瘤对替莫唑胺的耐药性。","authors":"Bo Wang, Pengfei Xue, Rongrong Li, Yaxin Liang, Zhaohao Wang, Lili Yan, Qianqian Zhang, Conghui Tian, Lili Yi, Cuncun Yang, Xin Li, Juan Zheng","doi":"10.1186/s12935-025-03986-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Glioma is the most common primary malignant brain tumor in adults. Temozolomide (TMZ) represents a standard-of-care chemotherapeutic agent in glioblastoma (GBM). However, the development of drug resistance constitutes a significant hurdle in the treatment of malignant glioma. Elucidating the mechanisms of temozolomide (TMZ) resistance in glioma is of critical clinical importance for improving patient prognosis and developing novel therapeutic strategies.</p><p><strong>Methods: </strong>We obtained RNA sequencing (RNA-seq) data of 648 glioma samples from The Cancer Genome Atlas (TCGA) and 325 samples from the Chinese Glioma Genome Atlas (CGGA) as study cohorts. Additionally, we validated the expression characteristics of the NR2F6 gene in our in-house cohort of glioma patients. Furthermore, we investigated the potential mechanism of NR2F6 in TMZ resistance in glioma by constructing TMZ-resistant cell lines in vitro. Statistical analyses and graphical work were primarily performed using R language and GraphPad Prism software.</p><p><strong>Results: </strong>We observed a significant upregulation of NR2F6 expression in high-grade gliomas, which is associated with an unfavorable prognosis in patients. Concurrently, our findings revealed a significant upregulation of NR2F6 in drug-resistant cells, which induced TMZ resistance in glioma cells via the E2F2-PARP1 axis.</p><p><strong>Conclusion: </strong>In brief, NR2F6, as a nuclear transcription factor, enhances the transcription of E2F2.The increased expression of E2F2 enhances PARP1 expression, which in turn facilitates TMZ-mediated DNA damage repair, thereby diminishing glioma sensitivity to TMZ.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"366"},"PeriodicalIF":6.0000,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NR2F6 regulates Temozolomide resistance in glioma via the E2F2-PARP1 pathway.\",\"authors\":\"Bo Wang, Pengfei Xue, Rongrong Li, Yaxin Liang, Zhaohao Wang, Lili Yan, Qianqian Zhang, Conghui Tian, Lili Yi, Cuncun Yang, Xin Li, Juan Zheng\",\"doi\":\"10.1186/s12935-025-03986-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Glioma is the most common primary malignant brain tumor in adults. Temozolomide (TMZ) represents a standard-of-care chemotherapeutic agent in glioblastoma (GBM). However, the development of drug resistance constitutes a significant hurdle in the treatment of malignant glioma. Elucidating the mechanisms of temozolomide (TMZ) resistance in glioma is of critical clinical importance for improving patient prognosis and developing novel therapeutic strategies.</p><p><strong>Methods: </strong>We obtained RNA sequencing (RNA-seq) data of 648 glioma samples from The Cancer Genome Atlas (TCGA) and 325 samples from the Chinese Glioma Genome Atlas (CGGA) as study cohorts. Additionally, we validated the expression characteristics of the NR2F6 gene in our in-house cohort of glioma patients. Furthermore, we investigated the potential mechanism of NR2F6 in TMZ resistance in glioma by constructing TMZ-resistant cell lines in vitro. Statistical analyses and graphical work were primarily performed using R language and GraphPad Prism software.</p><p><strong>Results: </strong>We observed a significant upregulation of NR2F6 expression in high-grade gliomas, which is associated with an unfavorable prognosis in patients. Concurrently, our findings revealed a significant upregulation of NR2F6 in drug-resistant cells, which induced TMZ resistance in glioma cells via the E2F2-PARP1 axis.</p><p><strong>Conclusion: </strong>In brief, NR2F6, as a nuclear transcription factor, enhances the transcription of E2F2.The increased expression of E2F2 enhances PARP1 expression, which in turn facilitates TMZ-mediated DNA damage repair, thereby diminishing glioma sensitivity to TMZ.</p>\",\"PeriodicalId\":9385,\"journal\":{\"name\":\"Cancer Cell International\",\"volume\":\"25 1\",\"pages\":\"366\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12935-025-03986-6\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03986-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：神经胶质瘤是成人最常见的原发性恶性脑肿瘤。替莫唑胺（TMZ）是胶质母细胞瘤（GBM）的标准治疗化疗药物。然而，耐药性的发展构成了恶性胶质瘤治疗的重大障碍。阐明替莫唑胺（TMZ）在胶质瘤中的耐药机制对改善患者预后和开发新的治疗策略具有重要的临床意义。方法：获取来自The Cancer Genome Atlas （TCGA）的648份胶质瘤样本和来自Chinese glioma Genome Atlas （CGGA）的325份样本的RNA测序（RNA-seq）数据作为研究队列。此外，我们验证了NR2F6基因在胶质瘤患者内部队列中的表达特征。此外，我们通过体外构建TMZ耐药细胞株，探讨NR2F6在胶质瘤TMZ耐药中的潜在机制。统计分析和图形化工作主要使用R语言和GraphPad Prism软件进行。结果：我们观察到NR2F6在高级别胶质瘤中的表达显著上调，这与患者的不良预后相关。同时，我们的研究结果揭示了耐药细胞中NR2F6的显著上调，通过E2F2-PARP1轴诱导胶质瘤细胞对TMZ的耐药。结论：总之，NR2F6作为一种核转录因子，可以促进E2F2的转录。E2F2表达的增加增强了PARP1的表达，进而促进TMZ介导的DNA损伤修复，从而降低胶质瘤对TMZ的敏感性。
NR2F6 regulates Temozolomide resistance in glioma via the E2F2-PARP1 pathway.
Background: Glioma is the most common primary malignant brain tumor in adults. Temozolomide (TMZ) represents a standard-of-care chemotherapeutic agent in glioblastoma (GBM). However, the development of drug resistance constitutes a significant hurdle in the treatment of malignant glioma. Elucidating the mechanisms of temozolomide (TMZ) resistance in glioma is of critical clinical importance for improving patient prognosis and developing novel therapeutic strategies.
Methods: We obtained RNA sequencing (RNA-seq) data of 648 glioma samples from The Cancer Genome Atlas (TCGA) and 325 samples from the Chinese Glioma Genome Atlas (CGGA) as study cohorts. Additionally, we validated the expression characteristics of the NR2F6 gene in our in-house cohort of glioma patients. Furthermore, we investigated the potential mechanism of NR2F6 in TMZ resistance in glioma by constructing TMZ-resistant cell lines in vitro. Statistical analyses and graphical work were primarily performed using R language and GraphPad Prism software.
Results: We observed a significant upregulation of NR2F6 expression in high-grade gliomas, which is associated with an unfavorable prognosis in patients. Concurrently, our findings revealed a significant upregulation of NR2F6 in drug-resistant cells, which induced TMZ resistance in glioma cells via the E2F2-PARP1 axis.
Conclusion: In brief, NR2F6, as a nuclear transcription factor, enhances the transcription of E2F2.The increased expression of E2F2 enhances PARP1 expression, which in turn facilitates TMZ-mediated DNA damage repair, thereby diminishing glioma sensitivity to TMZ.
期刊介绍：
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
