title: Specific delivery of microRNA93 into HBV-replicating hepatocytes downregulates protein expression of liver cancer susceptible gene MICA.
abstract: Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). To date, the lack of efficient in vitro systems supporting HBV infection and replication has been a major limitation of HBV research. Although primary human hepatocytes support the complete HBV life cycle, their limited availability and difficulties with gene transduction remain problematic. Here, we used human primary hepatocytes isolated from humanized chimeric uPA/SCID mice as efficient sources. These hepatocytes supported HBV replication in vitro. Based on analyses of mRNA and microRNA (miRNA) expression levels in HBV-infected hepatocytes, miRNA93 was significantly downregulated during HBV infection. MiRNA93 is critical for regulating the expression levels of MICA protein, which is a determinant for HBV-induced HCC susceptibility. Exogenous addition of miRNA93 in HBV-infected hepatocytes using bionanocapsules consisted of HBV envelope L proteins restored MICA protein expression levels in the supernatant. These results suggest that the rescued suppression of soluble MICA protein levels by miRNA93 targeted to HBV-infected hepatocytes using bionanocapsules may be useful for the prevention of HBV-induced HCC by altering deregulated miRNA93 expression.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; These authors contributed equally to this work.
authors.forename: Motoko
authors.initials: M
authors.lastname: Ohno
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Japan Science and Technology Agency, PRESTO, Kawaguchi, Saitama, Japan; These authors contributed equally to this work.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kishikawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Shibata
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Takata
authors.affiliation: Unit of Disease Control Genome Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Muroyama
authors.affiliation: Unit of Disease Control Genome Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Norie
authors.initials: N
authors.lastname: Kowatari
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sato
authors.affiliation: Unit of Disease Control Genome Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002678:Chimera; D015536:Down-Regulation; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000821:virology; D022781:Hepatocytes / Q000502:physiology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics; D014779:Virus Replication
chemical_list: D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C543350:MIRN93 microRNA, human; D035683:MicroRNAs