Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma.
Nat Med
; 19(2): 209-16, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23291631
ABSTRACT
A better understanding of human hepatocellular carcinoma (HCC) pathogenesis at the molecular level will facilitate the discovery of tumor-initiating events. Transcriptome sequencing revealed that adenosine-to-inosine (AâI) RNA editing of AZIN1 (encoding antizyme inhibitor 1) is increased in HCC specimens. AâI editing of AZIN1 transcripts, specifically regulated by ADAR1 (encoding adenosine deaminase acting on RNA-1), results in a serine-to-glycine substitution at residue 367 of AZIN1, located in ß-strand 15 (ß15) and predicted to cause a conformational change, induced a cytoplasmic-to-nuclear translocation and conferred gain-of-function phenotypes that were manifested by augmented tumor-initiating potential and more aggressive behavior. Compared with wild-type AZIN1 protein, the edited form has a stronger affinity to antizyme, and the resultant higher AZIN1 protein stability promotes cell proliferation through the neutralization of antizyme-mediated degradation of ornithine decarboxylase (ODC) and cyclin D1 (CCND1). Collectively, AâI RNA editing of AZIN1 may be a potential driver in the pathogenesis of human cancers, particularly HCC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Edição de RNA
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Nat Med
Ano de publicação:
2013
Tipo de documento:
Article