MicroRNAs, wild-type and mutant p53: more questions than answers.
The tumor suppressor p53 is a sequence-specific transcription factor that activates the expression of genes involved in apoptosis, cell cycle arrest and senescence. p53 can also inhibit gene expression and this effect is partly mediated by inducing several microRNAs (miRNAs). MiRNAs have emerged as a new class of regulators of the expression and function of eukaryotic genomes. Tumor suppressive or oncogenic functions have been attributed to some miRNAs. Recent studies have shown that p53 can alter the transcription of several miRNAs, and in some cases, it can also influence miRNA maturation. Conversely, miRNAs can also modulate the abundance and activity of p53 by direct or indirect mechanisms. Moreover, mutant p53 can actively repress the expression of some miRNAs that are activated by wild-type p53. In this review, we discuss recent evidences of this crosstalk between miRNAs and the p53 network and also highlight its implications in cancer.
Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Matthew
M
Jones
Ashish
A
Lal
D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D035683:MicroRNAs; D050505:Mutant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53