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Negative regulation of tumor suppressor p53 by microRNA miR-504.

ABSTRACT: 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.

SUBMITTER: Hu W

PROVIDER: S-EPMC2900922 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Negative regulation of tumor suppressor p53 by microRNA miR-504.

Hu Wenwei W Chan Chang S CS Wu Rui R Zhang Cen C Sun Yvonne Y Song Jun S JS Tang Laura H LH Levine Arnold J AJ Feng Zhaohui Z

Molecular cell 20100601 5

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 ...[more]

PMID: 20542001

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