Document Detail


Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma.
MedLine Citation:
PMID:  23291631     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-06
Journal Detail:
Title:  Nature medicine     Volume:  19     ISSN:  1546-170X     ISO Abbreviation:  Nat. Med.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-07     Completed Date:  2013-04-17     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  209-16     Citation Subset:  IM    
Affiliation:
Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Adenosine Deaminase / physiology
Animals
Carcinoma, Hepatocellular / etiology,  genetics*
Carrier Proteins / genetics*
Cell Line, Tumor
Cell Proliferation
Cyclin D1 / metabolism
Humans
Liver Neoplasms / etiology,  genetics*
Male
Mice
Ornithine Decarboxylase / metabolism
RNA Editing*
Grant Support
ID/Acronym/Agency:
P01 CA066996/CA/NCI NIH HHS; R01 CA118316/CA/NCI NIH HHS; R01 HL056745/HL/NHLBI NIH HHS; R01 HL112719/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/AZIN1 protein, human; 0/CCND1 protein, human; 0/Carrier Proteins; 136601-57-5/Cyclin D1; EC 3.5.4.-/dsRNA adenosine deaminase; EC 3.5.4.4/Adenosine Deaminase; EC 4.1.1.17/Ornithine Decarboxylase
Comments/Corrections
Comment In:
Cancer Discov. 2013 Mar;3(3):OF12   [PMID:  23475882 ]
Nat Med. 2013 Feb;19(2):130-1   [PMID:  23389604 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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