Negative Regulation of Tumor Suppressor p53 by MicroRNA miR-504

Wenwei Hu, Chang S. Chan, Rui Wu, Cen Zhang, Yvonne Sun, Jun S. Song, Laura H. Tang, Arnold J. Levine, Zhaohui Feng

Research output: Contribution to journalArticlepeer-review


Tumor suppressor p53 plays a central role in tumor prevention. p53 protein levels and activity are under a tight and complex regulation in cells to maintain the proper function of p53. MicroRNAs play a key role in the regulation of gene expression. Here we report the regulation of p53 through miR-504. miR-504 acts as a negative regulator of human p53 through its direct binding to two sites in the p53 3′ untranslated region. Overexpression of miR-504 decreases p53 protein levels and functions in cells, including p53 transcriptional activity, p53-mediated apoptosis, and cell-cycle arrest in response to stress, and furthermore promotes tumorigenecity of cells in vivo. These results demonstrate the direct negative regulation of p53 by miR-504 as a mechanism for p53 regulation in cells, which highlights the importance of microRNAs in tumorigenesis.

Original languageEnglish (US)
Pages (from-to)689-699
Number of pages11
JournalMolecular cell
Issue number5
StatePublished - Jun 11 2010
Externally publishedYes


  • DNA
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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