Negative regulation of the tumor suppressor p53 gene by microRNAs
摘要：
The tumor suppressor p53, encoded by theTP53gene, 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 reports have revealed that several microRNAs (miRNAs) are important components of the p53 tumor suppressor network with miR-125b and miR-504 directly targetingTP53. In this report, we use a screening method to identify that two miRNAs (miR-25 and miR-30d) directly target the 3'UTR ofTP53to down-regulate 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 littleTP53mutations. Thus, beyond miR-125b and miR-504, the humanTP53gene is negatively regulated by two more miRNAs: miR-25 and miR-30d.
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DOI：
10.1038/onc.2010.457
被引量：
年份：
2011
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