Please use this identifier to cite or link to this item: https://doi.org/10.1038/nm.3043
Title: Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma
Authors: Chen, L. 
Li, Y.
Lin, C.H.
Chan, T.H.M.
Chow, R.K.K.
Song, Y.
Liu, M.
Yuan, Y.-F.
Fu, L.
Kong, K.L.
Qi, L. 
Li, Y.
Zhang, N.
Tong, A.H.Y.
Kwong, D.L.-W.
Man, K.
Lo, C.M.
Lok, S.
Tenen, D.G. 
Guan, X.-Y.
Issue Date: Feb-2013
Citation: Chen, L., Li, Y., Lin, C.H., Chan, T.H.M., Chow, R.K.K., Song, Y., Liu, M., Yuan, Y.-F., Fu, L., Kong, K.L., Qi, L., Li, Y., Zhang, N., Tong, A.H.Y., Kwong, D.L.-W., Man, K., Lo, C.M., Lok, S., Tenen, D.G., Guan, X.-Y. (2013-02). Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. Nature Medicine 19 (2) : 209-216. ScholarBank@NUS Repository. https://doi.org/10.1038/nm.3043
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 β-strand 15 (β15) 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. © 2013 Nature America, Inc. All rights reserved.
Source Title: Nature Medicine
URI: http://scholarbank.nus.edu.sg/handle/10635/126290
ISSN: 10788956
DOI: 10.1038/nm.3043
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