| Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. | |
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MedLine Citation:
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PMID: 23291631 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Leilei Chen; Yan Li; Chi Ho Lin; Tim Hon Man Chan; Raymond Kwok Kei Chow; Yangyang Song; Ming Liu; Yun-Fei Yuan; Li Fu; Kar Lok Kong; Lihua Qi; Yan Li; Na Zhang; Amy Hin Yan Tong; Dora Lai-Wan Kwong; Kwan Man; Chung Mau Lo; Si Lok; Daniel G Tenen; Xin-Yuan Guan |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-06 |
Journal Detail:
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Title: Nature medicine Volume: - ISSN: 1546-170X ISO Abbreviation: Nat. Med. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9502015 Medline TA: Nat Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. [2] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [3] State Key Laboratory of Liver Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. [4]. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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