| 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. © 2010 Elsevier Inc. All rights reserved. |
| Keywords: |
controlled study; unclassified drug; human cell; histopathology; nonhuman; solid tumor; protein function; mouse; animals; mice; animal tissue; cell cycle; apoptosis; microrna; stress, physiological; animal experiment; animal model; protein binding; in vivo study; transcription, genetic; cancer cell culture; cell line, tumor; protein p53; mice, inbred balb c; rna; dna; regulatory mechanism; genetic transfection; mice, nude; western blotting; carcinogenicity; tumor suppressor protein p53; cell cycle arrest; binding site; cellcycle; binding sites; genes, reporter; real time polymerase chain reaction; 3' untranslated region; micrornas; cell strain mcf 7; gene knockdown techniques; cell transplantation; cell stress; cell strain hct116; 3' untranslated regions; microrna 504
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