PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism.

Hepatocellular carcinoma (HCC) necessitates innovative prognostic biomarkers and therapeutic targets. By investigating PNMA1 in HCC via the TCGA and GEO databases and our clinical data, we found that its overexpression is associated with worse survival. The relevance of PNMA1 extends to immune factors such as M1 macrophages, CD8 T cells, and immune checkpoints. Mechanistically, PNMA1 shapes a suppressive tumor microenvironment strongly linked to bile acid metabolism. It promotes tumor progression via immune inhibition and PI3K-AKT pathway activation. Notably, PNMA1 has emerged as a promising therapeutic target for tyrosine kinase inhibitors, as confirmed by reduced IC50 values and molecular docking. Experimental knockdown of PNMA1 hindered HepG2 cell proliferation and migration. Furthermore, PNMA1 is a pivotal HCC biomarker and therapeutic target with a focus on cancer progression, immune modulation, and bile acid metabolism.