Interestingly however, the KD of BHLHE40 rather further enhances p-AKT levels and p-p70S6K as a downstream factor of AKT although cellular senescence levels are decreased by the KD (Fig. 1O, P) suggesting that BHLHE40 rather inhibits the AKT signaling, which may be one tumor suppressive pathway mediated by BHLHE40. This evidence concerns the gene RPS6KB1 and neoplasm.