Elucidation of the enhanced IFN action by the non-coding RNA and its application on HCV treatment

• Project/Area Number: 24590956
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: YOSHIDA Haruhiko 東京大学, 医学部附属病院, 登録研究員 (60240305)
• Co-Investigator(Kenkyū-buntansha): OTSUKA Motoyuki 東京大学, 医学部附属病院消化器内科, 助教 (90518945)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: IFN / 非コードRNA / HCV / インターフェロン / microRNA / SOCS3 / エピジェネティクス

Outline of Final Research Achievements

miR122 was identified as an enhancer of IFN action. miR122 enhanced methylation of the SOCS3 DNA promoter and decreased its expression, which enhances IFN signaling. Apigenin decreases miR122 expression. Therefore, cotreatment of IFN and apigenin may be useful for the inhibition of HCV replication through the augmentation of IFN signaling.

Research Products

• [Journal Article] Diagnostic and therapeutic application of noncoding RNAs for hepatocellular carcinoma. (2015)
  • Author(s): Shibata C, Otsuka M, Kishikawa T, Ohno M, Yoshikawa T, Takata A, Koike K.
  • Journal Title: World J Hepatol. Volume: 7 Pages: 1-6
  • Peer Reviewed / Open Access
• [Journal Article] Decreased miR122 in hepatocellular carcinoma leads to chemoresistance with increased arginine (2015)
  • Author(s): Kishikawa T, Otsuka M, Tan PS, Ohno M, Sun X, Yoshikawa T, Shibata C, Takata A, Kojima K, Takehana K, Ohishi M, Ota S, Noyama T, Kondo Y, Sato M, Soga T, Hoshida Y, Koike K.
  • Journal Title: Oncotarget. Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels. (2014)
  • Author(s): Shibata C, Ohno M, Otsuka M, Kishikawa T, Goto K, Muroyama R, Kato N, Yoshikawa T, Takata A, Koike K.
  • Journal Title: Virology Volume: 462-463 Pages: 42-48
  • DOI: 10.1016/j.virol.2014.05.024
  • Peer Reviewed
• [Journal Article] Regulation of the expression of the liver cancer susceptibility gene MICA by microRNAs. (2013)
  • Author(s): Kishikawa T, Otsuka M, Yoshikawa T, Ohno M, Takata A, Shibata C, Kondo Y, Akanuma M, Yoshida H, Koike K.
  • Journal Title: Sci Rep. Volume: 3 Issue: 1 Pages: 2739-2739
  • DOI: 10.1038/srep02739
  • Peer Reviewed
• [Journal Article] Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model. (2013)
  • Author(s): Yoshikawa T, Otsuka M, Kishikawa T, Takata A, Ohno M, Shibata C, Kang YJ, Yoshida H, Koike K.
  • Journal Title: PLoS One. Volume: 8(9) Issue: 9 Pages: e71969-e71969
  • DOI: 10.1371/journal.pone.0071969
  • Peer Reviewed
• [Journal Article] Inhibition of microRNA122 decreases SREBP1 expression by modulating suppressor of cytokine signaling 3 expression. (2013)
  • Author(s): Shibata C, Kishikawa T, Otsuka M, Ohno M, Yoshikawa T, Takata A, Yoshida H, Koike K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 438(1) Issue: 1 Pages: 230-5
  • DOI: 10.1016/j.bbrc.2013.07.064
  • Peer Reviewed
• [Journal Article] Perihepatic lymph node enlargement is a negative predictor for sustained responses to pegylated interferon-α and ribavirin therapy for Japanese patients infected with hepatitis C virus genotype 1. (2013)
  • Author(s): Yoshida H et al. (16人中4番目)
  • Journal Title: Hepatol Res. Volume: Epub Issue: 10 Pages: 1005-1012
  • DOI: 10.1111/hepr.12061
  • Peer Reviewed
• [Journal Article] Meta-analysis: mortality and serious adverse events of peginterferon plus ribavirin therapy for chronic hepatitis C. (2013)
  • Author(s): Yoshida H et al. (6人中5番目)
  • Journal Title: J Gastroenterol. Volume: 48 Issue: 2 Pages: 254-68
  • DOI: 10.1007/s00535-012-0631-y
  • NAID: 10031156311
  • Peer Reviewed
• [Journal Article] Silencing of microRNA-122 enhances interferon- α signaling in the liver through regulating SOCS3 promoter methylation (2012)
  • Author(s): Otsuka M
  • Journal Title: Sci Rep Volume: 2 Issue: 1 Pages: 637-637
  • DOI: 10.1038/srep00637
  • Peer Reviewed
• [Journal Article] MicroRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression (2012)
  • Author(s): Otsuka M
  • Journal Title: Hepatology Volume: 57 Issue: 1 Pages: 162
  • DOI: 10.1002/hep.26011
  • Peer Reviewed
• [Journal Article] Increased activity of serum mitochondrial isoenzyme of creatine kinase in hepatocellular carcinoma patients predominantly with recurrence (2012)
  • Author(s): Soroida Y, Ohkawa R, Nakagawa H, Satoh Y, Yoshida H, Kinoshita H, Tateishi R, Masuzaki R, Enooku K, Shiina S, Sato T, Obi S, Hoshino T, Nagatomo R, Okubo S, Yokota H, Koike K, Yatomi Y, Ikeda H
  • Journal Title: J Hepatol Volume: 57 Issue: 2 Pages: 330
  • DOI: 10.1016/j.jhep.2012.03.012
  • Peer Reviewed
• [Remarks] 研究グループのホームページ
  • URL: https://sites.google.com/site/225kenncrna/