Integrated bioinformatics analysis of m6A/m7G/m5C/m1A RNA methylation-related genes in ulcerative colitis

Ulcerative colitis (UC), a primary subtype of inflammatory bowel disease, remains incompletely understood in terms of its molecular etiology. This study aimed to characterize the gene signatures associated with m6A, m7G, m5C, and m1A RNA modifications and explore their potential role in UC pathogenesis. We integrated three GEO datasets and, via LASSO regression, random forest, and SVM-RFE algorithms, identified three core differentially expressed RNA methylation-related genes (DERMGs): upregulated IFIT5 and MSI2 and downregulated NCBP1. These biomarkers showed diagnostic capability in the training cohort, with area under the curve (AUC) values above 0.75. The nomogram incorporating all three markers achieved an AUC of 0.947, with robust performance maintained in both the testing set and an additional external validation cohort. Functional enrichment analysis revealed that IFIT5 and MSI2 expression was positively correlated, whereas NCBP1 expression was inversely correlated with key inflammatory pathways, such as TNFA signaling via NF-κB, the inflammatory response, IL6/JAK/STAT3 signaling, and apoptosis. Immune infiltration assessment revealed that the expression of the core DERMGs was primarily associated with T cell subsets, as further supported by partial correlation analysis controlling for inflammatory burden. In addition, changes in the expression of these genes corresponded with clinical remission after treatment with infliximab or vedolizumab. In vitro experiments confirmed that LPS stimulation upregulated IFIT5 and MSI2 and downregulated NCBP1 in NCM460 and Caco-2 colonic epithelial cells. Collectively, these findings highlight the involvement of RNA methylations in UC pathogenesis and suggest IFIT5, MSI2, and NCBP1 as potential diagnostic and therapeutic targets.