Negative Regulation of Tumor Suppressor p53 by MicroRNA miR-504

Tumor suppressor p53 plays a central role in tumor prevention. p53 protein levels and activity are under a tight and complex regulation in cells to maintain the proper function of p53. MicroRNAs play a key role in the regulation of gene expression. Here we report the regulation of p53 through miR-504. miR-504 acts as a negative regulator of human p53 through its direct binding to two sites in the p53 3′ untranslated region. Overexpression of miR-504 decreases p53 protein levels and functions in cells, including p53 transcriptional activity, p53-mediated apoptosis, and cell-cycle arrest in response to stress, and furthermore promotes tumorigenecity of cells in vivo. These results demonstrate the direct negative regulation of p53 by miR-504 as a mechanism for p53 regulation in cells, which highlights the importance of microRNAs in tumorigenesis. ► miR-504 binds to two sites in human p53 3′UTR ► miR-504 reduces p53 protein levels and transcriptional activity ► miR-504 inhibits p53-mediated apoptosis and cell-cycle arrest ► miR-504 promotes tumorigenicity of cells in vivo