Oncogenic RBM19 modulated by MAX-mediated allelic transcription regulation in hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC), the most common type of liver cancer, exhibits the highest incidence in Asia and Africa. However, the mechanisms underlying the malignant transformation of normal cells to HCC cells remain poorly understood. MYC-associated protein X (MAX) functions as an oncogenic transcription factor (TF) in HCC by binding to E-box elements in promoters or enhancers of target gene. Using our previously developed Updated Integrative Functional Genomics Approach (TUIFGA), we identified 248 single nucleotide polymorphisms (SNPs) within MAX-binding sites in HCC cells. Among these SNPs, rs2290798 in the RBM19 promoter was significantly associated with HBV-related HCC risk. Functional assays indicated that the rs2290798 genetic variant could disrupt TF MAX binding to the RBM19 promoter and downregulate RBM19 expression. RBM19 acts as an oncogenic RNA-binding protein (RBP) through promoting proliferation, migration, and invasion of HCC cells. Indeed, RBM19 functions as a RBP via stabilizing several oncogenic transcripts (C1QTNF6, GLS1, MALAT1 or RBM19) and elevating their expression levels in HCC. These findings highlight the curial role of RBM19 in HCC progression and its potential as a therapeutic target in cancers.