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Suppression of host cellular microRNA functions by hepatitis C virus infection and its possible implication in hepatocarcinogenesis

Research Project

Project/Area Number 15K09035
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionJikei University School of Medicine (2016-2017)
National Institute of Infectious Diseases (2015)

Principal Investigator

MASAKI Takahiro  東京慈恵会医科大学, 医学部, 講師 (60535657)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsHCV / microRNA / miR-122 / miRISC / 肝発癌 / C型肝炎ウイルス / マイクロRNA
Outline of Final Research Achievements

The aims of this study were to test whether HCV affects the ability of microRNAs (miRNAs), including miR-122, to repress their endogenous targets, and if so, to address the underlying mechanism(s). The results showed that HCV infection led to increases in the expression of endogenous miRNA targets. This de-repression of miRNA targets was canceled in HCV subgenomic replicon (SGR) cells by supplementation of exogenous mature miRNAs. However, miRNA functions remained impaired in HCV-infected cells, suggesting the possible involvement of viral structural proteins in miRNA dysfunction. Interestingly, this miRNA dysfunction was reproduced in SGR cells by knocking down some of miRNA-induced silencing complex (miRISC) proteins, while overexpression of these proteins restored miRNA functions in HCV-infected cells. These results suggest that HCV structural proteins may induce the dysfunction of miRISC, resulting in the global de-repression of miRNA targets.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (37 results)

All 2018 2017 2016 2015

All Journal Article (11 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (24 results) (of which Int'l Joint Research: 8 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid2018

    • Author(s)
      Qin XY, Suzuki H, Honda M, Okada H, Kaneko S, Inoue I, Ebisui E, Hashimoto K, Carninci P, Kanki K, Tatsukawa H, Ishibashi N, Masaki T, Matsuura T, Kagechika H, Toriguchi K, Hatano E, Shirakami Y, Shiota G, Shimizu M, Moriwaki H, Kojima S
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 115 Issue: 19 Pages: 4969-4974

    • DOI

      10.1073/pnas.1802279115

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alpha-1 antichymotrypsin is involved in astrocyte injury in concert with arginine-vasopressin during the development of acute hepatic encephalopathy2017

    • Author(s)
      Park J, Masaki T, Mezaki Y, Yokoyama H, Nakamura M, Maehashi H, Fujimi TJ, Gouraud SS, Nagatsuma K, Nakagomi M, Kimura N, Matsuura T
    • Journal Title

      PLoS One

      Volume: 12 Issue: 12 Pages: e0189346-e0189346

    • DOI

      10.1371/journal.pone.0189346

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interferon sensitivity-determining region of hepatitis C virus influences virus production and interferon signaling2017

    • Author(s)
      Sugiyama R., Murayama A., Nitta S., Yamada N., Tasaka-Fujita M., Masaki T., Aly H. H., Shiina M., Ryo A., Ishii K., Wakita T. and Kato T.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 5 Pages: 5627-5640

    • DOI

      10.18632/oncotarget.23562

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 東京都立墨東病院の感染症科外来患者における糞便からのESBL産生腸内細菌の検出状況について2017

    • Author(s)
      西原弘人,小林謙一郎,阪本直也,岩渕千太郎,河野緑,政木隆博,松浦知和
    • Journal Title

      医学検査

      Volume: 66 Pages: 141-146

    • NAID

      130005509360

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] バイオ人工肝臓開発から臨床検査医学へ -空腹時 13C-glucose呼気試験の開発-2016

    • Author(s)
      松浦知和,目崎喜弘,政木隆博,松本喜弘,前橋はるか,中村まり子,中田浩二,朴ジョンヒョク,横山寛
    • Journal Title

      臨床病理

      Volume: 64 Pages: 558-563

    • Related Report
      2016 Research-status Report
  • [Journal Article] Effects of resistance-associated NS5A mutations in hepatitis C virus on viral production and susceptibility to antiviral reagents.2016

    • Author(s)
      Nitta S, Asahina Y, Matsuda M, Yamada N, Sugiyama R, Masaki T, Suzuki R, Kato N, Watanabe M, Wakita T, Kato T.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 34652-34652

    • DOI

      10.1038/srep34652

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NS5A phosphorylation: its functional role in the life cycle of hepatitis C virus2015

    • Author(s)
      Masaki T, Suzuki T
    • Journal Title

      Future Virol

      Volume: 10 Issue: 6 Pages: 751-762

    • DOI

      10.2217/fvl.15.33

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Protease inhibitors block multiple functions of the NS3/4A protease-helicase during the hepatitis C virus life cycle2015

    • Author(s)
      McGivern DR, Masaki T, Lovell W, Hamlett C, Saalau-Bethell S, Graham B
    • Journal Title

      J Virol

      Volume: 89 Issue: 10 Pages: 5362-5370

    • DOI

      10.1128/jvi.03188-14

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The yin and yang of hepatitis C: synthesis and decay of hepatitis C virus RNA2015

    • Author(s)
      Li Y, Yamane D, Masaki T, Lemon SM
    • Journal Title

      Nat Rev Microbiol

      Volume: 13 Issue: 9 Pages: 544-558

    • DOI

      10.1038/nrmicro3506

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Amino acid polymorphisms in hepatitis C virus core affect infectious virus production and major histocompatibility complex class I molecule expression2015

    • Author(s)
      Tasaka-Fujita M, Sugiyama N, Kang W, Masaki T, Murayama A, Yamada N, Sugiyama R, Tsukuda S, Watashi K, Asahina Y, Sakamoto N, Wakita T, Shin EC, Kato T
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 13994-14002

    • DOI

      10.1038/srep13994

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] microRNA-122によるC型肝炎ウイルスの複製制御2015

    • Author(s)
      政木隆博、Lemon SM
    • Journal Title

      ウイルス

      Volume: 65 Pages: 277-286

    • NAID

      130005250046

    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] C型肝炎ウイルスはmicroRNA-induced silencing complexを標的として宿主microRNA機能を抑制する2017

    • Author(s)
      政木隆博,加藤孝宣,脇田隆字,松浦知和
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肝疾患患者における線維新生マーカーTGF-β LAP断片の検討2017

    • Author(s)
      横山寛,政木隆博,小嶋聡一,松浦知和
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 急性肝不全に伴う致死的肝性脳症の発症機序の解明と新規診断・治療法の開発に向けた基礎的検討2017

    • Author(s)
      朴ジョンヒョク,政木隆博,目崎喜弘,横山寛,中村まり子,前橋はるか,松浦知和
    • Organizer
      第43回日本急性肝不全研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Hepatitis C virus attenuates host cellular microRNA functions by targeting the microRNA-induced silencing complex2017

    • Author(s)
      Masaki T, Mezaki Y, Matsuura T
    • Organizer
      The 29th World Congress of WASPaLM2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Alpha-1 antichymotrypsin is involved in astrocyte injury during the development of acute hepatic encephalopathy2017

    • Author(s)
      Park J, Masaki T, Mezaki Y, Yokoyama H, Nakamura M, Maehashi H, Matsuura T
    • Organizer
      The 29th World Congress of WASPaLM2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TGF-β LAP degradation products reflect fibrogenesis in patients with chronic liver disease2017

    • Author(s)
      Yokoyama H, Mezaki Y, Masaki T, Nakamura M, Park J, Kojima S, Matsuura T
    • Organizer
      The 29th World Congress of WASPaLM2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血液培養から分離されたHelicobacter属菌の菌株特性と臨床的特徴に関する検討2017

    • Author(s)
      河野緑,政木隆博,秋月摂子,中田浩二,大西明弘,海渡健,松浦知和
    • Organizer
      第64回日本臨床検査医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ホッキョクグマ肝臓レチノールエステル化酵素の生化学的および組織学的解析2016

    • Author(s)
      目崎喜弘,永妻啓介,横山寛,朴ジョンヒョク,中村まり子,政木隆博,妹尾春樹,松浦知和
    • Organizer
      第30回肝類洞壁細胞研究会学術集会
    • Place of Presentation
      富山
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] NASHの線維化におけるTGF-βLAP断片R58抗体発現の意義2016

    • Author(s)
      横山寛,目崎喜弘,政木隆博,中村まり子,朴ジョンヒョク,松本喜弘,永妻啓介,原詳子,井上育代,小嶋聡一,松浦知和
    • Organizer
      第30回肝類洞壁細胞研究会学術集会
    • Place of Presentation
      富山
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Hepatitis C virus targets the microRNA-induced silencing complex and attenuates host cellular microRNA functions2016

    • Author(s)
      Masaki T, Kato T, Mezaki Y, Nakamura M, Matsuura T, Wakita T
    • Organizer
      23rd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      京都
    • Year and Date
      2016-10-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Amino acid substitutions in IFN sensitivity-determining region of HCV-NS5A affect infectious virus production and ISG induction2016

    • Author(s)
      Sugiyama R, Sugiyama N, Murayama A, Tasaka-Fujita M, Yamada N, Nitta S, Masaki T, Ishii K, Ryo A, Wakita T, Kato T
    • Organizer
      23rd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      京都
    • Year and Date
      2016-10-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脂肪肝における肝臓インスリン抵抗性と空腹時13C-glucose呼気試験による評価2016

    • Author(s)
      松浦知和,政木隆博
    • Organizer
      第71回日本体力医学会大会
    • Place of Presentation
      盛岡
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Induction of NTCP expression in a human HCC cell line by retinoic acid and its effect on host susceptibility to HBV infection2016

    • Author(s)
      Masaki T, Matsumoto Y, Aizaki H, Nagamori S, Watashi K, Park J, Kanai Y, Kojima S, Wakita T, Matsuura T
    • Organizer
      2016 International HBV Meeting
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-09-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] C型肝炎ウイルス感染における宿主マイクロRNAの網羅的発現プロファイリングと機能解析2016

    • Author(s)
      政木隆博,目崎喜弘,松浦知和
    • Organizer
      第63回日本臨床検査医学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
  • [Presentation] 非アルコール性脂肪性肝炎の肝病理組織におけるTGF-βLAP-Dの分布とその意義2016

    • Author(s)
      横山寛,永妻啓介,白井美佐子,目崎喜弘,政木隆博,朴ジョンヒョク,小嶋聡一,松浦知和
    • Organizer
      第63回日本臨床検査医学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
  • [Presentation] 慢性肝疾患における肝線維新生マーカーTGF-βLAP-Dと肝線維化マーカーM2BPGiの継時測定2016

    • Author(s)
      松浦知和,目崎喜弘,横山寛,永妻啓介,政木隆博,小嶋聡一
    • Organizer
      第63回日本臨床検査医学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
  • [Presentation] C型肝炎ウイルスによる宿主microRNA機能抑制の分子機構2016

    • Author(s)
      政木隆博,加藤孝宣,脇田隆字
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      千葉
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Inhibition of host cellular microRNA functions by hepatitis C virus infection2015

    • Author(s)
      政木隆博、加藤孝宣、脇田隆字
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Attenuation of MHC class I expression by intracellular accumulation of HCV core protein2015

    • Author(s)
      加藤孝宣、藤田めぐみ、杉山奈央、政木隆博、村山麻子、脇田隆字
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Suppression of host cellular microRNA functions by HCV infection and its implication in the aggressiveness of hepatocellular carcinoma cells2015

    • Author(s)
      Masaki T, Kato T, Wakita T
    • Organizer
      22nd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Strasbourg, France
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Amino acid polymorphisms in HCV core affect infectious virus production and MHC class I molecule expression2015

    • Author(s)
      Tasaka-Fujita M, Sugiyama N, Kang W, Masaki T, Murayama A, Wakita T, Shin EC, Kato T
    • Organizer
      22nd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Strasbourg, France
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] microRNA-122によるC型肝炎ウイルスゲノム複製の新規制御機構2015

    • Author(s)
      政木隆博、加藤孝宣、脇田隆字
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] C型肝炎ウイルスISDR変異によるインターフェロン耐性発現機序の解析2015

    • Author(s)
      加藤孝宣、政木隆博、脇田隆字
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] HCV感染培養系を用いたDaclatasvir耐性変異株の抗HCV薬に対する薬剤感受性の評価2015

    • Author(s)
      新田沙由梨、村山麻子、藤田めぐみ、山田典栄、政木隆博、脇田隆字、朝比奈靖浩、加藤孝宣
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Book] Annual Review 消化器 20162016

    • Author(s)
      政木隆博、加藤孝宣
    • Total Pages
      247
    • Publisher
      中外医学社
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] Alpha-1 アンチキモトリプシンを含むバイオマーカー2017

    • Inventor(s)
      松浦知和,朴ジョンヒョク,政木隆博
    • Industrial Property Rights Holder
      松浦知和,朴ジョンヒョク,政木隆博
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-111441
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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