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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 |
Appears in Collections: | Staff Publications |
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