利用多中心研究的集成分析,为胶质瘤建立基于RNA甲基化相关的长链非编码RNA风险分层系统。
Using integrated analysis from multicentre studies to identify RNA methylation-related lncRNA risk stratification systems for glioma.
发表日期:2023 Aug 05
作者:
Fanxuan Huang, Xinyu Wang, Junzhe Zhong, Hao Chen, Dan Song, Tianye Xu, Kaifu Tian, Penggang Sun, Nan Sun, Jie Qin, Yu Song, Wenbin Ma, Yuxiang Liu, Daohan Yu, Xiangqi Meng, Chuanlu Jiang, Hanwen Xuan, Da Qian, Jinquan Cai
来源:
Cellular & Molecular Immunology
摘要:
N6-甲基腺苷(m6A)、5-甲基胞苷(m5C)和N1-甲基腺苷(m1A)是与癌症发展相关的主要RNA甲基化修饰。然而,RNA甲基化相关的长链非编码RNA(lncRNA)是否影响胶质瘤的预后仍不清楚。我们总结了32个m6A/m5C/m1A相关基因,并从癌症基因组图谱(TCGA)数据库下载了RNA测序数据和临床信息。利用差异表达分析和加权基因共表达网络分析(WGCNA),筛选出差异表达(DE-)RNA甲基化相关的lncRNA,以构建胶质瘤的预后标志并确定其与免疫功能、免疫治疗和药物敏感性的相关性。进行体外和体内实验以阐明RNA甲基化相关lncRNA对胶质瘤的影响。共计十个RNA甲基化相关lncRNA用于构建一个具有良好独立预测能力的生存和预后标志。结果显示,在所有队列中,高风险组的总生存期较低风险组更短。此外,风险组与不同亚组胶质瘤患者的免疫功能、免疫治疗响应以及药物敏感性密切相关。在体外和体内实验中,下调RP11-98I9.4和RP11-752G15.8诱导更具侵袭性的表型,促进细胞增长并表现明显的对替莫唑胺(TMZ)的耐药性。我们观察到胶质瘤细胞中全局的RNA m5C和m6A水平明显升高。研究确定了与胶质瘤相关的RNA甲基化相关lncRNA的预后意义,建立了一个与RNA甲基化相关的lncRNA预测模型,并阐明了RP11-98I9.4和RP11-752G15.8能够抑制胶质瘤增殖、迁移和对TMZ的抗药性。未来,这些RNA甲基化相关lncRNA可能成为胶质瘤免疫治疗的新选择。© 2023年。BioMed Central Ltd.,Springer Nature的一部分。
N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether RNA methylation-related long noncoding RNAs (lncRNAs) affect the prognosis of glioma.We summarized 32 m6A/m5C/m1A-related genes and downloaded RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify differentially expressed (DE-) RNA methylation-related lncRNAs in order to construct a prognostic signature of glioma and in order to determine their correlation with immune function, immune therapy and drug sensitivity. In vitro and in vivo assays were performed to elucidate the effects of RNA methylation-related lncRNAs on glioma.A total of ten RNA methylation-related lncRNAs were used to construct a survival and prognosis signature, which had good independent prediction ability for patients. It was found that the high-risk group had worse overall survival (OS) than the low-risk group in all cohorts. In addition, the risk group informed the immune function, immunotherapy response and drug sensitivity of patients with glioma in different subgroups. Knockdown of RP11-98I9.4 and RP11-752G15.8 induced a more invasive phenotype, accelerated cell growth and apparent resistance to temozolomide (TMZ) both in vitro and in vivo. We observed significantly elevated global RNA m5C and m6A levels in glioma cells.Our study determined the prognostic implication of RNA methylation-related lncRNAs in gliomas, established an RNA methylation-related lncRNA prognostic model, and elucidated that RP11-98I9.4 and RP11-752G15.8 could suppress glioma proliferation, migration and TMZ resistance. In the future, these RNA methylation-related lncRNAs may become a new choice for immunotherapy of glioma.© 2023. BioMed Central Ltd., part of Springer Nature.