title: ADAR2-mediated editing of miR-214 and miR-122 precursor and antisense RNA transcripts in liver cancers.
abstract: A growing list of microRNAs (miRNAs) show aberrant expression patterns in hepatocellular carcinoma (HCC), but the regulatory mechanisms largely remain unclear. RNA editing catalyzed by members of the adenosine deaminase acting on the RNA (ADAR) family could target the miRNA precursors and affect the biogenesis process. Therefore, we investigate whether RNA editing could be one mechanism contributing to the deregulation of specific miRNAs in HCC. By overexpression of individual ADARs in hepatoma cells, RNA editing on the precursors of 16 miRNAs frequently deregulated in HCC was screened by a sensitive high-resolution melting platform. The results identified RNA precursors of miR-214 and miR-122 as potential targets edited by ADAR2. A subset of HCC showing elevated ADAR2 verified the major editings identified in ARAR2 overexpressed hepatoma cells, either with A-to-I or U-to-C changes. The unusual U-to-C editing at specific residues was demonstrated as being attributed to the A-to-I editing on the RNA transcripts complementary to the pri-miRNAs. The editing event caused a decrease of the RNA transcript complementary to pri-miR-214, which led to the decrease of pri-miR-214 and miR-214 and resulted in the increased protein level of its novel target gene Rab15. In conclusion, the current study discovered ADAR2-mediated editing of the complementary antisense transcripts as a novel mechanism for regulating the biogenesis of specific miRNAs during hepatocarcinogenesis.
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan ; National Taiwan University Center for Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wan-Hsin
authors.initials: WH
authors.lastname: Liu
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Kun-Huei
authors.initials: KH
authors.lastname: Yeh
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chiao-Ling
authors.initials: CL
authors.lastname: Li
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yi-Jinn
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan ; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan ; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan ; National Taiwan University Center for Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan ; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shiou-Hwei
authors.initials: SH
authors.lastname: Yeh
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D017393:RNA Editing; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: C531907:MIRN122 microRNA, human; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase