Integrated analysis from multicentre studies identities RNA methylation- related lncRNA risk stratification systems for glioma

Abstract

Abstract Background:N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m5C) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether RNA methylation-related long non-coding RNAs (lncRNAs) affect the prognosis of glioma. Methods:We summarized 32 m6A/m5C/m1A-related genes, 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) to identify associated with differential expression (DE-) RNA methylation-related lncRNAs to construct a prognostic signature of glioma and their correlation with immune function, immune therapy and drug sensitivity analyzed. In vitro and in vivo assays were performed to elucidate the effects of RNA methylation-related lncRNAs on glioma. Results:A total of ten RNA methylation-related lncRNAs were used to construct a survival and prognosis model, which had good independent prediction ability for patients. It was found that the high-risk group has worse overall survival (OS) than the low-risk group with all cohort. In addition, the risk group inform 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 identified significantly elevated global RNA m5C and m6A levels in glioma cells. Conclusion: Our study determined the prognostic implication of the RNA methylation-related lncRNAs in gliomas, established the RNA methylation-related lncRNAs prognostic model, and elucidated that RP11-98I9.4 and RP11-752G15.8 could suppressglioma proliferation, migration and TMZ-resistant. In the future, these RNA methylation-related lncRNA may become a new choice for immunotherapy of glioma.