The microRNA feedback regulation of p63 in cancer progression

Oncotarget. 2015 Apr 20;6(11):8434-53. doi: 10.18632/oncotarget.3020.

Abstract

The transcription factor p63 is a member of the p53 gene family that plays a complex role in cancer due to its involvement in epithelial differentiation, cell cycle arrest and apoptosis. MicroRNAs are a class of small, non-coding RNAs with an important regulatory role in various cellular processes, as well as in the development and progression of cancer. A number of microRNAs have been shown to function as transcriptional targets of p63. Conversely, microRNAs also can modulate the expression and activity of p63. However, the p63-microRNA regulatory circuit has not been addressed in depth so far. Here, computational genomic analysis was performed using miRtarBase, Targetscan, microRNA.ORG, DIANA-MICROT, RNA22-HSA and miRDB to analyze miRNA binding to the 3'UTR of p63. JASPAR (profile score threshold 80%) and TFSEARCH datasets were used to search transcriptional start sites for p53/p63 response elements. Remarkably, these data revealed 63 microRNAs that targeted p63. Furthermore, there were 39 microRNAs targeting p63 that were predicted to be regulated by p63. These analyses suggest a crosstalk between p63 and microRNAs. Here, we discuss the crosstalk between p63 and the microRNA network, and the role of their interactions in cancer.

Keywords: cancer; feedback; microRNA; p63.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing
  • Cell Transformation, Neoplastic / genetics
  • Computational Biology
  • Disease Progression
  • Feedback, Physiological
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Promoter Regions, Genetic / genetics
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Processing, Post-Transcriptional
  • RNA, Neoplasm / genetics
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcription Factors / physiology
  • Transcription, Genetic
  • Transcriptional Activation / genetics
  • Tumor Suppressor Proteins / biosynthesis
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / physiology

Substances

  • MicroRNAs
  • Neoplasm Proteins
  • Protein Isoforms
  • RNA, Neoplasm
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins