Tumor suppressor p53 plays a central role in tumor suppression. As a 
transcription factor, p53 mainly exerts its tumor suppressive function through 
transcriptional regulation of many target genes. To maintain the proper function 
of p53, p53 protein level and activity are exquisitely controlled by a group of 
positive and negative regulators in cells. Thus, p53, its regulators, and 
regulated genes form a complicated p53 signaling network. microRNAs (miRNAs) are 
a group of endogenous small non-coding RNA molecules. miRNAs play an important 
role in regulation of gene expression by blocking translational protein 
synthesis and/or degrading target mRNAs. Recent studies have demonstrated that 
p53 and its network are regulated by miRNAs at multiple levels. Some miRNAs 
regulate the level and function of p53 through directly targeting p53, whereas 
some other miRNAs target regulators of p53, such as MDM2 and MDM4, to indirectly 
regulate the activity and function of p53. On the other hand, p53 also regulates 
the transcriptional expression and the biogenesis of a group of miRNAs, which 
contributes to the tumor suppressive function of p53. p53 is the most frequently 
mutated gene in human cancer. Many tumor-associated mutant p53, which have 
"gain-of-function" activities in tumorigenesis independently of wild type p53, 
can regulate the expression of different miRNAs and modulate the biogenesis of 
specific miRNAs to promote tumorigenesis. These findings have demonstrated that 
miRNAs are important regulators and mediators of p53 and its signaling pathway, 
which highlights a pivotal role of miRNAs in the p53 network and cancer. J. 
Cell. Biochem. 118: 7-14, 2017. © 2016 Wiley Periodicals, Inc.