PRMT3 drives PD-L1-mediated immune escape through activating PDHK1-regulated glycolysis in hepatocellular carcinoma.

ABSTRACT: Aberrant expression of programmed death ligand-1 (PD-L1) facilitates tumor immune evasion. Protein arginine methyltransferase 3 (PRMT3), a member of type I PRMT family, mediates asymmetric dimethylarginine (ADMA) modification of various substrate proteins. This study investigates the role of PRMT3 in PD-L1-associated tumor immunosuppression in hepatocellular carcinoma (HCC). Hepatocyte-specific knockout of Prmt3 significantly suppressed HCC progression in DEN-CCL₄-treated mice. Knockout of Prmt3 in HCC cells markedly increased CD8⁺ T cell infiltration, and reduced lactate production in tumors. PRMT3 interacted with pyruvate dehydrogenase kinase 1 (PDHK1), asymmetric dimethylation of PDHK1 at arginine 363 and 368 residues and increased its kinase activity. The R363/368

SUBMITTER: Ding CH 

PROVIDER: S-EPMC11885674 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature