PRMT2 promotes tumorigenic phenotypes through the Wnt signaling pathway and drives immune suppression in Colorectal cancer.

Abstract

Protein arginine methyltransferase 2 (PRMT2) is a critical epigenetic modulator that orchestrates diverse biological processes through histone methylation-dependent transcriptional regulation. While previous studies have established its pro-inflammatory role in murine colitis, the oncogenic functions and immunomodulatory mechanisms of PRMT2 in colorectal cancer (CRC) pathogenesis remain elusive. In this study, integrated analysis of TCGA database, colorectal cancer single-cell database, and CRC patient-derived tissue microarrays revealed significant upregulation of PRMT2 in tumor tissues, which correlated with adverse clinical outcomes and reduced survival rates. Mechanistically, we found that PRMT2 can promote the transcriptional expression of WNT5A, thereby activating the Wnt/β-catenin signaling pathway and malignant progression of CRC. Notably, our study uncovered the dual immunoregulatory role of PRMT2 in shaping the tumor microenvironment. PRMT2 not only induced M2-like polarization of tumor-associated macrophages (TAMs) but also impaired anti-tumor T cell responses by promoting CD4⁺/CD8⁺ T cell dysfunction. In conclusion, our findings position PRMT2 as a multifaceted therapeutic target that simultaneously addresses tumor intrinsic malignancy and microenvironmental immunosuppression in CRC.