Elucidation of the mechanisms of HBV infection using single cell transcriptome analysis

• Project/Area Number: 16K15426
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: HONDA Masao 金沢大学, 保健学系, 教授 (00272980)
• Co-Investigator(Kenkyū-buntansha): 橋本 真一 金沢大学, 医薬保健学総合研究科, 特任教授 (00313099)
• Co-Investigator(Renkei-kenkyūsha): SHIRASAKI Takayoshi 金沢大学, 保健学系, 助教 (50547180) ; KAWAGUCHI Kazunori 金沢大学, 附属病院, 助教 (90579632)
• Research Collaborator: Oishi Naoki
• Project Period (FY): 2016-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: ウイルス / 遺伝子 / 感染症 / 発現制御 / ウィルス

Outline of Final Research Achievements

We identified two essential host genes for HBV replication by using single cell transcriptome analysis of KM cells that were established from a HCC tissue derived from a patient with chronic hepatitis B. Repression of two genes reduced cccDNA, and by the combination of ETV, more than 95% reduction of cccDNA was obtained. By using HepG2-NTCP cells in which two genes were knocked down, primary human hepatocytes (PXB) and HepG2-NTCP cells in which two genes were overexpressed by lentivirus system, we showed HBV-DNA, cccDNA and pgRNA were substantially changed by the expression of two genes.

Research Products

• [Journal Article] De Novo Emergence of Mesenchymal Stem-Like CD105+ Cancer Cells by Cytotoxic Agents in Human Hepatocellular Carcinoma. (2017)
  • Author(s): Nomura Y, Yamashita T, Oishi N, Nio K, Hayashi T, Yoshida M, Hayashi T, Hashiba T, Asahina Y, Okada H, Sunagozaka H, Takatori H, Honda M, Kaneko S.
  • Journal Title: Transl Oncol. Volume: - Issue: 2 Pages: 184-189
  • DOI: 10.1016/j.tranon.2017.01.005
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection. (2017)
  • Author(s): Matsuura K, Honda M, et al.
  • Journal Title: Gastroenterology. Volume: - Issue: 6 Pages: 1383-1394
  • DOI: 10.1053/j.gastro.2017.01.041
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Branched-chain amino acids prevent hepatic fibrosis and development of hepatocellular carcinoma in a non-alcoholic steatohepatitis mouse model. (2017)
  • Author(s): K Takegoshi, M Honda, H Okada, R Takabatake, N Matsuzawa-Nagata, JS Campbell, M Nishikawa, T Shimakami, T Shirasaki, Y Sakai, T Yamashita, T Takamura, T Tanaka, S Kaneko.
  • Journal Title: Oncotarget Volume: 印刷中 Issue: 11 Pages: 18191-18205
  • DOI: 10.18632/oncotarget.15304
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle. (2017)
  • Author(s): H Misu, H Takayama, Y Saito, Y Mita, A Kikuchi, K Ishii, K Chikamoto, T Kanamori, N Tajima, F Lan, Y Takeshita, M Honda, M Tanaka, S Kato, N Matsuyama, Y Yoshioka, Iwayama K, Tokuyama K, Akazawa N, Maeda S, Takekoshi K, Matsugo S, Noguchi N, S Kaneko, T Takamura.
  • Journal Title: Nature Med Volume: 23 Issue: 4 Pages: 508-516
  • DOI: 10.1038/nm.4295
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population. (2017)
  • Author(s): Kawashima M, Honda M, Nakamura M. et al.
  • Journal Title: Hum Mol Genet. Volume: - Pages: 650-659
  • DOI: 10.1093/hmg/ddw406
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differential hepatitis C virus RNA target site selection and host factor activities of naturally occurring miR-122 3' variants. (2017)
  • Author(s): Yamane D, Selitsky SR, Shimakami T, Li Y, Zhou M, Honda M, Sethupathy P, Lemon SM.
  • Journal Title: Nucleic Acids Res. Volume: - Pages: 4743-4755
  • DOI: 10.1093/nar/gkw1332
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics. (2016)
  • Author(s): Kawaguchi K, Honda M, Kaneko S.
  • Journal Title: Transl Cancer Res. Volume: 5(S2) Issue: S2 Pages: S216-S220
  • DOI: 10.21037/tcr.2016.08.13
  • Peer Reviewed / Open Access
• [Journal Article] Response to chemotherapy improved hepatic reserve for patients with hepatocellular carcinoma and Child-Pugh B cirrhosis. (2016)
  • Author(s): Terashima T, Yamashita T, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
  • Journal Title: Cancer Sci. Volume: 107(9) Issue: 9 Pages: 1263-1269
  • DOI: 10.1111/cas.12992
  • NAID: 120005851362
  • Peer Reviewed / Open Access
• [Journal Article] Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems. (2016)
  • Author(s): Liu F, Shimakami T, Murai K, Shirasaki T, Funaki M, Honda M, Murakami S, Yi M, Tang H, Kaneko S.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 30939-30939
  • DOI: 10.1038/srep30939
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Jagged1 DNA Copy Number Variation Is Associated with Poor Outcome in Liver Cancer. (2016)
  • Author(s): Kawaguchi K, Honda M, Yamashita T, Okada H, Shirasaki T, Nishikawa M, Nio K, Arai K, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S.
  • Journal Title: Am J Pathol. Volume: 186(8) Issue: 8 Pages: 2055-2067
  • DOI: 10.1016/j.ajpath.2016.04.011
  • NAID: 120005899105
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Post-progression survival and progression-free survival in patients with advanced hepatocellular carcinoma treated by sorafenib. (2016)
  • Author(s): Terashima T, Yamashita T, Takata N, Nakagawa H, Toyama T, Arai K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
  • Journal Title: Hepatol Res. Volume: 印刷中 Issue: 7 Pages: 650-656
  • DOI: 10.1111/hepr.12601
  • NAID: 120005704530
  • Peer Reviewed / Open Access
• [Journal Article] Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events. (2016)
  • Author(s): Takashima S, Usui S, Kurokawa K, Kitano T, Kato T, Murai H, Furusho H, Oda H, Maruyama M, Nagata Y, Usuda K, Kubota K, Takeshita Y, Sakai Y, Honda M, Kaneko S, Takamura M.
  • Journal Title: Open Heart. Volume: 3(1) Issue: 1 Pages: e000400-e000400
  • DOI: 10.1136/openhrt-2016-000400
  • NAID: 120005830627
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Potential efficacy of therapies targeting intrahepatic lesions after sorafenib treatment of patients with hepatocellular carcinoma. (2016)
  • Author(s): Yamashita T, Horii R, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
  • Journal Title: BMC Cancer. Volume: 16(1) Issue: 1 Pages: 338-338
  • DOI: 10.1186/s12885-016-2380-4
  • Peer Reviewed / Open Access
• [Journal Article] Molecular Mechanism Underlying the Suppression of CPB2 Expression Caused by Persistent Hepatitis C Virus RNA Replication. (2016)
  • Author(s): Sejima H, Satoh S, Dansako H, Honda M, Kaneko S, Ikeda M, Kato N.
  • Journal Title: Acta Med Okayama. Volume: 70(2) Pages: 75-88
  • NAID: 120005749825
  • Peer Reviewed / Open Access
• [Journal Article] Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis. (2016)
  • Author(s): N. Nishida (他37名, 山本31番目)
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 24767-24767
  • DOI: 10.1038/srep24767
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatitis B Virus (HBV) Core-Related Antigen During Nucleos(t)ide Analog Therapy Is Related to Intra-hepatic HBV Replication and Development of Hepatocellular Carcinoma. (2016)
  • Author(s): Honda M, Shirasaki T, Terashima T, Kawaguchi K, Nakamura M, Oishi N, Wang X, Shimakami T, Okada H, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S.
  • Journal Title: J Infect Dis Volume: 213 Issue: 7 Pages: 1096-1106
  • DOI: 10.1093/infdis/jiv572
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] C型肝細胞癌根治治療後の肝炎ウイルス治療の 意義と宿主因子 (2016)
  • Author(s): 本多政夫、方堂祐治、金子周一
  • Organizer: JDDW2016
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2016-11-03
• [Presentation] Pyruvate kinase muscle (PKM)の肝炎・肝癌病態における役割 (2016)
  • Author(s): 本多政夫、岡田 光、金子周一
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ幕張（千葉県千葉市）
  • Year and Date: 2016-05-19
• [Presentation] インスリン抵抗性因子セレノプロテインP（SeP)のHCV複製及び自然免疫応答に与える影響 (2016)
  • Author(s): 本多政夫、村居和寿、金子周一
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-04-21
• [Presentation] Innate immunity during HCV infection (2016)
  • Author(s): 本多政夫
  • Organizer: The 3rd International symposium on viral Hepatitis
  • Place of Presentation: 成都（中国）
  • Int'l Joint Research