PSRC1 facilitates hepatocellular carcinoma progression by regulating KIF2A-associated Wnt/β-catenin signaling

Hepatocellular carcinoma (HCC) remains a major therapeutic challenge owing to its aggressive nature and limited treatment options. This study therefore investigated the biological function and regulatory mechanism of PSRC1 in HCC. WGCNA, differential expression analysis, and LASSO Cox regression were used to select candidate genes. PSRC1 expression was determined by qRT-PCR and Western blot. The effects of PSRC1 on HCC cell behavior were evaluated using CCK-8, colony formation, Transwell, and flow cytometric assays. Wnt/β-catenin activity was examined using nuclear–cytoplasmic fractionation, immunofluorescence microscopy, and pathway inhibition. Co-immunoprecipitation and rescue experiments were performed to investigate the interaction and functional relationship between PSRC1 and KIF2A. Bioinformatic screening revealed PSRC1 as a survival-associated gene with upregulated expression in HCC tissues. PSRC1 expression was elevated in HCC cell lines, and higher PSRC1 expression was associated with unfavorable outcomes. Loss of PSRC1 not only restrained the growth and motility of HCC cells but also potentiated apoptosis and induced cell-cycle arrest. Notably, this depletion decreased β-catenin levels in both cytosolic and nuclear fractions, which subsequently dampened downstream Wnt/β-catenin signaling. Co-IP confirmed an interaction between PSRC1 and KIF2A. Overexpression of KIF2A partially alleviated the phenotypic and signaling changes induced by PSRC1 knockdown. PSRC1 promotes HCC development, at least in part, through regulation of KIF2A -dependent Wnt/β-catenin signaling. These findings suggest that PSRC1 may represent a potential molecular regulator and therapeutic target in HCC.