miR-34a repression of SIRT1 regulates apoptosis

Munekazu Yamakuchi, Marcella Ferlito, Charles J. Lowenstein

Research output: Contribution to journalArticle

Abstract

MicroRNA 34a (miR-34a) is a tumor suppressor gene, but how it regulates cell proliferation is not completely understood. We now show that the microRNA miR-34a regulates silent information regulator 1 (SIRT1) expression. MiR-34a inhibits SIRT1 expression through a miR-34a-binding site within the 3′ UTR of SIRT1. MiR-34 inhibition of SIRT1 leads to an increase in acetylated p53 and expression of p21 and PUMA, transcriptional targets of p53 that regulate the cell cycle and apoptosis, respectively. Furthermore, miR-34 suppression of SIRT1 ultimately leads to apoptosis in WT human colon cancer cells but not in human colon cancer cells lacking p53. Finally, miR-34a itself is a transcriptional target of p53, suggesting a positive feedback loop between p53 and miR-34a. Thus, miR-34a functions as a tumor suppressor, in part, through a SIRT1-p53 pathway.

Original languageEnglish (US)
Pages (from-to)13421-13426
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number36
DOIs
StatePublished - Sep 9 2008

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Keywords

  • Cancer
  • microRNA
  • p53

ASJC Scopus subject areas

  • Genetics
  • General

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