STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Genes Dev
; 26(13): 1459-72, 2012 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-22751500
ABSTRACT
Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI protein associates with and leads to the stabilization of miR-20a; miR-20a, in turn, regulates TGFßR2 and the TGFß signaling network. This pathway circuitry is substantiated by in silico epistasis analysis of its components in the human GBM TCGA (The Cancer Genome Atlas Project) collection and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53-QKI-miR-20a-TGFß pathway expands our understanding of the p53 tumor suppression network in cancer and reveals a novel tumor suppression mechanism involving regulation of specific cancer-relevant microRNAs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linhagem Celular
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Proteínas de Ligação a RNA
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Glioblastoma
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Estabilidade de RNA
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MicroRNAs
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Genes Dev
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos