RB1 and hepatocellular carcinoma: For instance, CBX4 functions as a tumor suppressor by inhibiting the c-myc expression and cellular transformation9; CBX4 connects with E2F and Rb to repress the transcription of both cyclin A and cdc2, which consequently reduce cell proliferation, this function is involved in its PRC1 complex10; and CBX4 positively regulates proliferation, angiogenesis, and cancer metastasis in hepatocellular carcinoma (HCC), which is dependent on in its sumoylating E3 activity6,11.