Negative regulation of the tumor suppressor p53 gene by microRNAs

M. Kumar, Z. Lu, A. A.L. Takwi, W. Chen, N. S. Callander, K. S. Ramos, K. H. Young, Y. Li

Research output: Contribution to journalArticle

186 Scopus citations

Abstract

The tumor suppressor p53, encoded by the TP53 gene, is recognized as the guardian of the human genome because it regulates many downstream genes to exercise its function in cell cycle and cell death. Recent studies have revealed that several microRNAs (miRNAs) are important components of the p53 tumor suppressor network with miR-125b and miR-504 directly targeting TP53. In this study, we use a screening method to identify that two miRNAs (miR-25 and miR-30d) directly target the 3′UTR of TP53 to downregulate p53 protein levels and reduce the expression of genes that are transcriptionally activated by p53. Correspondingly, both miR-25 and miR-30d adversely affect apoptotic cell death, cell cycle arrest and cellular senescence. Inhibition of either miR-25 or miR-30d expression increases endogenous p53 expression and elevates cellular apoptosis in several cell lines, including one from multiple myeloma that has little TP53 mutations. Thus, beyond miR-125b and miR-504, the human TP53 gene is negatively regulated by two more miRNAs: miR-25 and miR-30d.

Original languageEnglish (US)
Pages (from-to)843-853
Number of pages11
JournalOncogene
Volume30
Issue number7
DOIs
StatePublished - Feb 17 2011

Keywords

  • apoptosis
  • cell cycle arrest
  • microRNA
  • multiple myeloma
  • p53
  • senescence

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Kumar, M., Lu, Z., Takwi, A. A. L., Chen, W., Callander, N. S., Ramos, K. S., Young, K. H., & Li, Y. (2011). Negative regulation of the tumor suppressor p53 gene by microRNAs. Oncogene, 30(7), 843-853. https://doi.org/10.1038/onc.2010.457