TAF3 Promotes Tumor Progression of Hepatocellular Carcinoma via SREBP2-mediated Cholesterol Synthesis Pathway Activation

Here, we investigate TAF3’s functional role and mechanistic basis in HCC progression. Loss- and gain-of-function assays demonstrated that TAF3 significantly altered proliferation, invasion, and migration in HepG2 and MHCC97H cell lines.

Clinical analysis of 30 HCC specimens revealed that elevated TAF3 expression correlated strongly with larger tumor size, increased tumor number, microvascular invasion, advanced stage, poor differentiation, and worse prognosis. Mechanistically, comprehensive ChIP-seq and luciferase reporter assays identified sterol regulatory element-binding protein 2 (SREBP2) as a direct transcriptional target of TAF3. TAF3 bound the SREBP2 promoter, upregulating its expression and activating cholesterol biosynthesis.