1. Negative Regulation of Tumor Suppressor p53 by MicroRNA miR-504
- Author
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Arnold J. Levine, Cen Zhang, Rui Wu, Zhaohui Feng, Jun S. Song, Wenwei Hu, Laura H. Tang, Yvonne Sun, and Chang S. Chan
- Subjects
Transcription, Genetic ,Cell Transplantation ,Mice, Nude ,Apoptosis ,Biology ,medicine.disease_cause ,Article ,law.invention ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Genes, Reporter ,Stress, Physiological ,law ,Transcription (biology) ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,3' Untranslated Regions ,Molecular Biology ,030304 developmental biology ,Regulation of gene expression ,Mice, Inbred BALB C ,0303 health sciences ,Binding Sites ,Three prime untranslated region ,Cell Cycle ,Cell Biology ,Cell cycle ,Molecular biology ,Cell biology ,MicroRNAs ,Cell culture ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Suppressor ,Female ,Tumor Suppressor Protein p53 ,Carcinogenesis - 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.
- Published
- 2010