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p53 and microRNA-34 are suppressors of canonical Wnt signaling

Authors
 Nam Hee Kim  ;  Hyun Sil Kim  ;  Stephen J. Weiss  ;  Jong In Yook  ;  Barry M. Gumbiner  ;  Sanghyuk Lee  ;  Kunhong Kim  ;  Changbum Park  ;  Jung Min Na  ;  Joo Kyung Ryu  ;  So Young Cha  ;  Shi Eun Kang  ;  Xiao-Yan Li  ;  Hyung-Seok Choi  ;  Inhan Lee  ;  Nam-Gyun Kim 
Citation
 Science Signaling, Vol.4(197) : 71-71, 2011 
Journal Title
 Science Signaling 
ISSN
 1937-9145 
Issue Date
2011
Abstract
Although loss of p53 function and activation of canonical Wnt signaling cascades are frequently coupled in cancer, the links between these two pathways remain unclear. We report that p53 transactivated microRNA-34 (miR-34), which consequently suppressed the transcriptional activity of β-catenin-T cell factor and lymphoid enhancer factor (TCF/LEF) complexes by targeting the untranslated regions (UTRs) of a set of conserved targets in a network of genes encoding elements of the Wnt pathway. Loss of p53 function increased canonical Wnt signaling by alleviating miR-34-specific interactions with target UTRs, and miR-34 depletion relieved p53-mediated Wnt repression. Gene expression signatures reflecting the status of β-catenin-TCF/LEF transcriptional activity in breast cancer and pediatric neuroblastoma patients were correlated with p53 and miR-34 functional status. Loss of p53 or miR-34 contributed to neoplastic progression by triggering the Wnt-dependent, tissue-invasive activity of colorectal cancer cells. Further, during development, miR-34 interactions with the β-catenin UTR affected Xenopus body axis polarity and the expression of Wnt-dependent patterning genes. These data provide insight into the mechanisms by which a p53-miR-34 network restrains canonical Wnt signaling cascades in developing organisms and human cancer.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94627
DOI
10.1126/scisignal.2001744
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry & Molecular Biology (생화학-분자생물학교실)
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소)
Yonsei Authors
강시은(Kang, Shi Eun) ; 김건홍(Kim, Kun Hong) ; 김남희(Kim, Nam Hee) ; 김현실(Kim, Hyun Sil) ; 유주경(Ryu, Ju Kyoung) ; 육종인(Yook, Jong In) ; 차소영(Cha, So Young)
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