Title: Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma
Author: Chen, L.; Li, Y.; Lin, C. H. (...)
Source: Nat Med, 2013,
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 beta-strand 15 (beta15) 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.