Accumulating evidence supports the involvement of PRMT5 in cancer development; however, its cross-cancer molecular features remain incompletely characterized. Here, we performed an integrated pan-cancer analysis of PRMT5 and complemented the in silico results with PRMT5 knockdown experiments in three representative cancer cell lines. PRMT5 was upregulated in most cancers and showed cancer-type specific prognostic associations. Immune infiltration analysis revealed that PRMT5 expression was associated with an immunosuppressive microenvironment, characterized by reduced CD8+ T-cell levels in CESC and SKCM and elevated fibroblast recruitment across a broad spectrum of tumors, such as LIHC and PAAD. Enrichment analysis suggested that PRMT5-associated networks were linked to DNA/RNA metabolism and stress-response pathways. In vitro, PRMT5 silencing reduced proliferation, migration and stemness-associated features of carcinoma cells. Together, our analysis provides a cross-cancer resource for understanding PRMT5 and supports further evaluation of PRMT5 as a potential biomarker and therapeutic target in selected tumor contexts.
Kunpeng et al. (2026) studied this question.