SERBP1 promoter single nucleotide polymorphism (SNP) rs3762314: a genetic susceptibility biomarker promoting malignant phenotype in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. SERPINE1 mRNA binding protein 1 (SERBP1) has been implicated as an oncogenic factor in HCC; however, the role of SERBP1 single nucleotide polymorphisms (SNPs) in HCC susceptibility and progression remains unclear. This study aimed to identify functional regulatory SNPs in SERBP1 associated with HCC risk and progression. The SERBP1 rs3762314 T allele carriers (CT/TT genotypes) exhibited increased HCC susceptibility and were associated with distant metastasis, alcohol consumption history, elevated SERBP1 expression, and Ki67 proliferation index. Mechanistically, dual-luciferase reporter assays indicated that the T allele enhanced SERBP1 promoter activity, potentially through attenuation of CEBPα-mediated transcriptional repression. scRNA-seq analysis revealed that SERBP1+ HCC cells exhibited enhanced epithelial-mesenchymal transition (EMT) programs and proliferative signatures, which were validated by in vitro functional assays. These findings suggest that SERBP1 rs3762314 may serve as a potential genetic biomarker for HCC risk stratification, while SERBP1 represents a potential therapeutic target.