Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma
Leilei Chen,Yan Li,Chi Ho Lin,Tim Chan,Tim Chan,Raymond Kwok Kei Chow,Yangyang Song,Ming Liu,Yunfei Yuan,Li Fu,Kar Lok Kong,Lihua Qi,Na Zhang,Amy Hin Yan Tong,Dora L.W. Kwong,Kwan Man,Chung Mau Lo,Si Lok,Daniel G. Tenen,Xin Yuan Guan,Xin Yuan Guan +20 more
TLDR
This article showed that adenosine-to-inosine (A→I) RNA editing of AZIN1 (encoding antizyme inhibitor 1) is increased in hepatocellular carcinoma (HCC) specimens.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.read more
Citations
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A-to-I editing of coding and non-coding RNAs by ADARs
TL;DR: Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA, leading to reduced expression or altered function of mature miRNAs and certain microRNA precursors.
Journal ArticleDOI
Role of RNA modifications in cancer.
Isaia Barbieri,Tony Kouzarides +1 more
TL;DR: The evidence that RNA modification pathways are misregulated in cancer and suggests that they may be ideal targets for cancer therapy is presented.
Journal ArticleDOI
RADAR: a rigorously annotated database of A-to-I RNA editing
Gokul Ramaswami,Jin Billy Li +1 more
TL;DR: RADAR includes a comprehensive collection of A-to-I RNA editing sites identified in humans (Homo sapiens), mice and flies (Mus musculus) and flies, together with extensive manually curated annotations for each editing site.
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The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers.
Leng Han,Lixia Diao,Shuangxing Yu,Xiaoyan Xu,Xiaoyan Xu,Jie Li,Rui Zhang,Yang Yang,Yang Yang,Henrica M.J. Werner,Henrica M.J. Werner,A. Karina Eterovic,Yuan Yuan,Jun Li,Nikitha Nair,Rosalba Minelli,Yiu Huen Tsang,Lydia W.T. Cheung,Kang Jin Jeong,Jason Roszik,Zhenlin Ju,Scott E. Woodman,Yiling Lu,Kenneth L. Scott,Jin Billy Li,Gordon B. Mills,Han Liang +26 more
TL;DR: The effects of several cross-tumor nonsynonymous RNA editing events on cell viability are experimentally demonstrated and the evidence that RNA editing could selectively affect drug sensitivity is provided, highlighting RNA editing as an exciting theme for investigating cancer mechanisms, biomarkers, and treatments.
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A-to-I RNA editing — immune protector and transcriptome diversifier
Eli Eisenberg,Erez Y. Levanon +1 more
TL;DR: Next-generation sequencing technologies have enabled the comparison of editomes from multiple individuals and from multiple species and the results have changed the understanding of the extent and distribution of A-to-I editing and its role in evolution and disease.
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