Besides the upregulation of the E2F1–DP1 complex and cell cycle regulators, the downregulation of the tumor suppressors p53 and RB1 by the ISX–E2F1 axis in hepatoma cells and tumors further emphasized the tumorigenic activity of the ISX–E2F1 axis in HCC. The gene discussed is RB1; the disease is hepatocellular carcinoma.