title: c-Myc-mediated overexpression of miR-17-92 suppresses replication of hepatitis B virus in human hepatoma cells.
abstract: MicroRNAs (miRNAs) regulate post-transcriptional gene expression in various physiological and pathological processes, including viral infections. The miR-17-92 cluster encodes six miRNAs (miR-17-5p, miR-18a, miR-19a, miR-19b, miR-20a, and miR-92a-1) which are transactivated by c-Myc. Because hepatitis B virus transactivates c-Myc, the interaction between the miR-17-92 cluster and HBV replication was examined in this study. Inducing HBV replication in a human hepatoma cell line increased miR-17-5p, miR-20a and miR-92a-1 expression. HBV-induced overexpression of miR-17-92 was reversed by c-Myc knockdown. Antisense peptide nucleic acids against miR-20a and miR-92a-1 augmented HBV replication. A computational analysis yielded potential binding sites for miR-20a and miR-92a-1 in the HBV genome. The direct interaction between these two miRNAs and target regions in HBV transcripts was confirmed by luciferase reporter analysis. These results demonstrated negative feedback suppression of HBV replication by the miR-17-92 polycistron.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Jung
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Min
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jang
authors.forename: Nam Young
authors.initials: NY
authors.lastname: Kim
authors.forename: Sook-Hyang
authors.initials: SH
authors.lastname: Jeong
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Shin
authors.forename: Sang Hyub
authors.initials: SH
authors.lastname: Lee
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Hwang
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Lee
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor; D015870:Gene Expression; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014779:Virus Replication / Q000235:genetics*
chemical_list: C568997:MIR17HG, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding