NSUN2 as a therapeutic target: Modulating tumor growth and immune microenvironment in colon adenocarcinoma.

Elevated expression of the RNA methyltransferase NSUN2 is significantly associated with advanced disease progression and shorter overall survival in colorectal adenocarcinoma (COAD), underscoring its clinical relevance. To elucidate the functional and mechanistic role of NSUN2 in COAD, this study first analyzed its expression patterns, prognostic value, and correlations with clinicopathological features, oncogenic pathways, and immune infiltration using the TCGA-COAD cohort. Immunohistochemical staining further confirmed increased NSUN2 protein levels in clinical specimens. Genetic manipulation in cell lines and mouse models demonstrated that NSUN2 markedly enhances malignant phenotypes, including proliferation and migration, and promotes tumor growth and metastasis in vivo. Mechanistically, NSUN2 was found to drive tumor progression through two coordinated processes: activation of the Wnt/β-catenin signaling pathway, which directly facilitates cancer cell growth and invasion, and restriction of CD8+ T-cell infiltration into the tumor microenvironment, resulting in localized immunosuppression. These findings reveal the dual oncogenic function of NSUN2 in COAD-it not only propels tumor progression through direct signaling activation but also enables immune evasion by attenuating anti-tumor immunity. In summary, this study systematically clarifies how NSUN2 promotes COAD development by simultaneously activating the Wnt/β-catenin pathway and suppressing CD8+ T-cell-mediated immunity, providing a strong mechanistic foundation for its potential as a therapeutic target in future COAD treatment strategies.