Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma
| Autor: | Kwan Man, Kar Lok Kong, Daniel G. Tenen, Chi Ho Lin, Si Lok, Chung Mau Lo, Xin Yuan Guan, Lihua Qi, Li Fu, Yangyang Song, Raymond Kwok Kei Chow, Ming Liu, Na Zhang, Amy Hin Yan Tong, Tim Chan, Dora L.W. Kwong, Yunfei Yuan, Leilei Chen, Yan Li |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Carcinoma Hepatocellular Adenosine Deaminase Active Transport Cell Nucleus RNA-binding protein Ornithine Decarboxylase Article General Biochemistry Genetics and Molecular Biology Ornithine decarboxylase Mice Cyclin D1 Cell Line Tumor medicine Animals Humans Ornithine decarboxylase antizyme Cell Proliferation Antizyme inhibitor 1 biology Liver Neoplasms RNA-Binding Proteins General Medicine Molecular biology Cell nucleus medicine.anatomical_structure RNA editing ADAR Cancer research biology.protein RNA Editing Carrier Proteins |
| Zdroj: | Nature Medicine. 19:209-216 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm.3043 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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