Cross Talk between the Circadian Clock Proteins and TP53 in Cancer and Therapeutic Significance.

The circadian rhythms regulate physiological and cellular processes that maintain normal homeostasis, keeping our cells synchronized to the dark-light cycle. The disruption of circadian clock genes has been associated with various diseases, including cancer. The clock genes impact several cancer-related signaling trajectories, including the tumor suppressor's p53 pathway involvement in the regulation of the cell cycle and apoptosis. In most human cancers, p53 loses its normal functions and tumor-suppressive activity through function-inactivating mutations. Herein, we review the roles of each of the clock genes (PER1-3, CRY1/2, BMAL1, CLOCK, REV-ERBα/β, RORα, and SIRT1) in their association and regulation of p53. We analyzed by bioinformatics the expression of several clock genes (CLOCK, CRY1-2, PER1-3), p53, and apoptotic and metabolic genes across all tumors in the TCGA platform, and found deregulated patterns in many cases. Our findings support the development of new therapies targeted against some clock genes to restore p53 activities and the inhibition of tumor development. Such therapies will complement a large number of currently tested treatments targeting the restoration of wild-type p53 to prevent tumor growth and lead cancer cells to apoptosis.