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Title 

p53 and mMicroRNA-34 are suppressors of canonical Wnt signaling

Authors 

N H KimH S KimN G KimI LeeH S ChoiX Y LiS E KangS Y ChaJ K RyuJ M NaC ParkK KimSanghyuk LeeB M GumbinerJ I YookS J Weiss

Publisher 

American Association for the Advancement of Science

Issue Date 

2011

Citation 

Science Signaling, vol. 4, no. 197, pp. ra71-ra71

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.

ISSN 

1937-9145

Link 

http://dx.doi.org/10.1126/scisignal.2001744

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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