Bioinformatics Construction and Experimental Validation of a novel N6- Methylandenosine(m6A)-related lncRNA signature predicts prognosis and immune microenvironment in colon cancer

Abstract

Abstract Background Colon cancer is one of the most usual malignancies. which affects millions of people worldwide. M6A regulators play significant roles in oncogenesis, tumor progression and prognosis of cancers. The relevance of m6A-related lncRNAs in colon cancer has not been determined. Therefore, the data of transcriptome expression and clinical features were collected from the TCGA database. Methods Transcriptome data, miRNA-sequencing data, and clinical information were downloaded from the TCGA database. The m6A-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. Besides, the nomogram was built in view of the independent variables. Gene Set Enrichment Analysis (GSEA) and CIBERSORT algorithms were applied to evaluate the potential biological functions and to appraise the tumor microenvironment in the two risk groups, respectively. Moreover, the knockdown of m6A-related lncRNA was performed for in vitro analysis, as well as proliferation and colony formation assay. Results The result of Kaplan-Meier curve demonstrated remarkable differences in colon cancer patients' overall survival in the two risk groups in two cohorts. Receiver operating characteristic (ROC) curves were applied to appraise the manifestation of the model. Univariate and multivariate Cox regression analysis illustrated that the risk score was an independent prognostic factor in two cohorts. Prognosis-related lncRNA ITGB1-DT, SNHG26, AP006621.2, AL513550.1, and AP001619.1 were identified as prognostic risk variables. Knockdown of ITGB1-DT repressed colon cancer cells’ proliferation and colony formation. Conclusions This study indicates that m6A-related lncRNAs can function as the underlying independent prognostic biomarkers for colon cancer survival.