Mutant p53 exerts oncogenic effects through microRNAs and their target gene networks

Abstract

MicroRNAs are potent regulators of gene expression and modulate multiple cellular processes including proliferation, differentiation and apoptosis. A number of microRNAs have been shown to be regulated by p53, the most frequently mutated gene in human cancer. It is has been demonstrated that some mutant p53 proteins not only lose tumor suppressor activity, but also acquire novel oncogenic functions that are independent of wild-type p53. In this review, we highlight recent evidences suggesting that some mutant p53 proteins regulate the expression of specific microRNAs to gain oncogenic functions and identify a gene network regulated by the microRNAs downstream of mutant p53.

Keywords: Cancer; Gain-of-function; Invasion; Let-7; Metastasis; Mutant p53; miR-128-2; miR-130b; miR-155; miR-205; miR-223; miR-27a; miRNA; microRNA.

Fig. 1.

Mutant p53 regulates miRNAs to regulate a gene network. Mutant p53 activates or inhibits the expression of distinct miRNAs either directly or indirectly through interacting partners such as p63 or ZEB1. Altered expression of these miRNAs results in decreased expression of genes that play key roles in tumor progression, EMT and chemoresistance including MYC, LIN28B, NRAS, ZEB1 and E2F5.