N7-Methylguanosine (m7G) modification is important in post-transcriptional regulation. dysregulation of m7G RNA modification has been reported to be markedly associated with cancer. However, its importance in bladder urothelial carcinoma (BLCA) remains poorly characterized. The present study systematically analyzed mRNA gene expression data and clinical information from The Cancer Genome Atlas and further constructed robust risk signatures for the four regulators of m7G RNA modification (nudix hydrolase 11, gem nuclear organelle-associated protein 5, eukaryotic translation initiation factor 3 subunit D and cytoplasmic FMR1 interacting protein 1). The differential expression and cell function of m7G-related genes in bladder cancer cells were verified by reverse transcription-quantitative PCR, Cell Counting Kit-8 and colony formation assays. The four-gene-based model could accurately predict the prognosis of BLCA. Nomogram-based clinical decisions had a higher net benefit compared with that of individual predictors. Through immune infiltration analysis, it was found that immune cell infiltration affected the prognosis of patients with BLCA. Finally, the present study identified potential therapeutics that differ between high and low-risk groups based on four genes. In summary, the current findings revealed an essential role for m7G RNA modification regulators in BLCA, and developed risk signatures as promising prognostic markers in patients with BLCA.Copyright: © Zhang et al.