Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest

Cell Cycle. 2007 Jul 1;6(13):1586-93. doi: 10.4161/cc.6.13.4436. Epub 2007 May 11.


In a genome-wide screen for microRNAs regulated by the transcription factor encoded by the p53 tumor suppressor gene we found that after p53-activation the abundance of thirty-four miRNAs was significantly increased, whereas sixteen miRNAs were suppressed. The induction of miR-34a was most pronounced among all differential regulations. Also expression of the primary miR-34a transcript was induced after p53 activation and by DNA damage in a p53-dependent manner. p53 occupied an evolutionarily conserved binding site proximal to the first non-coding exon of miR-34a. Ectopic miR-34a induced apoptosis and a cell cycle arrest in the G1-phase, thereby suppressing tumor cell proliferation. Other p53-induced miRNAs identified here may also have tumor suppressive potential as they are known to suppress the anti-apoptotic factor Bcl2 (miR-15a/16) and the oncogenes RAS and HMGA2 (let-7a). Our results for the first time directly integrate the regulation of miRNA expression into the transcriptional network regulated by p53. siRNAs corresponding to p53-induced miRNAs may have potential as cancer therapeutic agents as RNA interference based therapies are currently emerging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Base Sequence
  • Chromosome Mapping
  • DNA Damage / genetics
  • G1 Phase / genetics*
  • Gene Expression Regulation*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / physiology*
  • Molecular Sequence Data
  • Sequence Analysis, RNA
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology*


  • MIRN34 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53

Associated data

  • GENBANK/EF570048
  • GENBANK/EF570049
  • GENBANK/EF606690
  • GENBANK/EF606691