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Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma.
- Source :
-
Nature Medicine . Feb2013, Vol. 19 Issue 2, p209-216. 8p. 6 Graphs. - Publication Year :
- 2013
-
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 (A?I) RNA editing of AZIN1 (encoding antizyme inhibitor 1) is increased in HCC specimens. A?I 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 ?-strand 15 (?15) 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, A?I RNA editing of AZIN1 may be a potential driver in the pathogenesis of human cancers, particularly HCC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 19
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 85337301
- Full Text :
- https://doi.org/10.1038/nm.3043