The role of the RB/E2F circuit in TERT regulation is supported by a recent report showing that the Human Krüppel related 3 (HKR3) is capable of repressing TERT gene expression in HCC cell lines, resulting in the subsequent activation of CDKN2A (encoding the p16 tumor suppressor factor) and cell cycle inhibition as a tumor suppressor mechanism [139]. This evidence concerns the gene CDKN2A and neoplasm.