The regulation of the p53/MDM2 feedback loop by microRNAs

DOI: 10.14800/rd.502

Abstract

Tumor suppressor p53 and its signaling pathway play a central role in tumor suppression. The E3 ubiquitin ligase MDM2, which is the most critical negative regulator of p53, forms an autoregulatory negative feedback loop with p53 in the cell to tightly regulate the levels and activity of p53. MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that play an important role in the post-translational regulation of gene expression. Recent studies have shown that miRNAs play an important role in regulating the p53 function in tumor suppression through directly regulating the levels of p53 or MDM2. Recently, we identified miR-339-5p as a new miRNA that directly represses MDM2 to activate p53 and enhance p53 function in tumor suppression. Thus, miRNAs have become an important component of the p53 signaling pathway through regulating the p53/MDM2 feedback loop.