Negative regulation of tumor suppressor p53 by microRNA miR-504.
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.
Hu
Wenwei
W
Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA.
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
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001665:Binding Sites; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D005260:Female; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; C550379:MIRN504 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53