Transcriptome-Wide Map of N⁶-Methyladenosine Methylome Profiling in Human Bladder Cancer

N⁶-Methyladenosine (m⁶A) is the most widespread internal RNA modification in several species. In spite of latest advances in researching the biological roles of m⁶A, its function in the development and progression of bladder cancer remains unclear. In this study, we used MeRIPty -55-seq and RNA-seq methods to obtain a comprehensive transcriptome-wide m⁶A profiling and gene expression pattern in bladder cancer and paired normal adjacent tissues. Our findings showed that there were 2,331 hypomethylated and 3,819 hypermethylated mRNAs, 32 hypomethylated and 105 hypermethylated lncRNAs, and 15 hypomethylated and 238 hypermethylated circRNAs in bladder cancer tissues compared to adjacent normal tissues. Furthermore, m⁶A is most often harbored in the coding sequence (CDS), with some near the start and stop codons between two groups. Functional enrichment analysis revealed that differentially methylated mRNAs, lncRNAs, and circRNAs were mostly enriched in transcriptional misregulation in cancer and TNF signaling pathway. We also found that different m⁶A methylation levels of gene might regulate its expression. In summary, our results for the first time provide an m⁶A landscape of human bladder cancer, which expand the understanding of m⁶A modifications and uncover the regulation of mRNAs, lncRNAs, and circRNAs through m⁶A modification in bladder cancer.