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    Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13421-6. Epub 2008 Aug 28.

    miR-34a repression of SIRT1 regulates apoptosis.

    Yamakuchi M, Ferlito M, Lowenstein CJ.

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    Departments of Medicine and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. myamaku1@jhmi.edu

    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.

    PMID:
    18755897
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2533205
    Free PMC Article

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