title: Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma.
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.
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Chi Ho
authors.initials: CH
authors.lastname: Lin
authors.forename: Tim Hon Man
authors.initials: TH
authors.lastname: Chan
authors.forename: Raymond Kwok Kei
authors.initials: RK
authors.lastname: Chow
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Song
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Yuan
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Kar Lok
authors.initials: KL
authors.lastname: Kong
authors.forename: Lihua
authors.initials: L
authors.lastname: Qi
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Amy Hin Yan
authors.initials: AH
authors.lastname: Tong
authors.forename: Dora Lai-Wan
authors.initials: DL
authors.lastname: Kwong
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
authors.forename: Chung Mau
authors.initials: CM
authors.lastname: Lo
authors.forename: Si
authors.initials: S
authors.lastname: Lok
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D021581:Active Transport, Cell Nucleus; D000243:Adenosine Deaminase / Q000502:physiology; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D017393:RNA Editing; D016601:RNA-Binding Proteins
chemical_list: C484011:AZIN1 protein, human; C530104:CCND1 protein, human; D002352:Carrier Proteins; D016601:RNA-Binding Proteins; D019938:Cyclin D1; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D009955:Ornithine Decarboxylase