• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The impact of the changes in serum exosomal miRNA profiles induced by DAAs therapy on liver carcinogenesis

Research Project

Project/Area Number 18K15820
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKumamoto University

Principal Investigator

Watanabe Takehisa  熊本大学, 大学院生命科学研究部(医), 助教 (20634843)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsmiRNA / DAAs / SVR / exosome / 癌 / 代謝異常 / HCV / 脂質代謝異常 / 肝発癌 / Exosome
Outline of Final Research Achievements

DAAs treatment has various effects on the organism other than the elimination of HCV. However, the mechanism is unknown. In this study, we comprehensively analyzed the changes in the expression profile of miRNAs in serum exosomes of HCV-infected patients before and after DAAs treatment and identified miRNAs whose expression was significantly decreased. These miRNAs are involved in hepato-carcinogenesis and lipid metabolism, suggesting their involvement in the pathogenesis after SVR. When HepG2 cells were treated with a specific inhibitor of the miRNA, the proliferation rate increased and lipid accumulation decreased. The miRNAs identified in this study are not only biomarkers but may lead to clinical applications such as drug discovery in the future.

Academic Significance and Societal Importance of the Research Achievements

肝疾患の診断において、侵襲的検査である肝生検による肝組織の採取が必要なケースがあるが、本研究に用いたexosomal miRNA 解析法は侵襲を伴わない体液診断法(Liquid biopsy)の1つとして、今後の肝疾患の臨床に大きく寄与しうるものである。DAAs 治療によりHCV-SVR 後患者の高齢化に伴い、発癌を含め今後SVR後の病態に関する知見はさらに必要になることが予想される。exosomal miRNA に着目した本研究は、単にバイオマーカーにとどまらず、SVR後の病態の解明、将来的には創薬等の臨床応用へ繋がる可能性がある。

Report

(3 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Modeling of the Weight Status and Risk of Nonalcoholic Fatty Liver Disease in Elderly Individuals: The Potential Impact of the Disulfide Bond-Forming Oxidoreductase A-Like Protein (DsbA-L) Polymorphism on the Weight Status.2018

    • Author(s)
      Oniki K, Watanabe T, Kudo M, Izuka T, Ono T, Matsuda K, Sakamoto Y, Nagaoka K, Imafuku T, Ishima Y, Watanabe H, Maruyama T, Otake K, Ogata Y, Saruwatari J.
    • Journal Title

      CPT:Pharmacometrics & Systems Pharmacology

      Volume: - Issue: 6 Pages: 384-393

    • DOI

      10.1002/psp4.12292

    • NAID

      120006937616

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Altered microRNA expression profiles in serum exosome links to clinical phenotypes induced by direct-acting antiviral therapy.2019

    • Author(s)
      Takehisa Watanabe, Nahoko Fujimoto, Katsuya Nagaoka, Satoshi Narahara, Kentaro Tanaka, Takayuki Tokunaga, Takeshi Kawasaki, Yoko Yoshimaru, Masakuni Tateyama, Hideaki Naoe, Motohiko Tanaka, and Yutaka Sasaki.
    • Organizer
      THE LIVER MEETING AASLD 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of the Changes of the Profiles of Exosomal miRNA in Serum of the Patients Induced By DAA Treatment.2018

    • Author(s)
      Takehisa Watanabe, Nahoko Fujimoto, Katsuya Nagaoka, Satoshi Narahara, Kentaro Tanaka, Takayuki Tokunaga, Takeshi Kawasaki, Youko Yoshimaru, Masakuni Tateyama, Hideaki Naoe, Motohiko Tanaka and Yutaka Sasaki.
    • Organizer
      The Liver Meeting (AASLD) 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当科における肝細胞癌根治例における抗ウイルス療法後の再発に関する検討2018

    • Author(s)
      立山雅邦、田中基彦、田中健太郎、楢原哲史、徳永尭之、川崎剛、吉丸洋子、渡邊丈久、佐々木裕.
    • Organizer
      第104回日本消化器病学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肝細胞癌に対するソラフェニブの治療効果を早期に予測する新規血清バイオマーカーの解析2018

    • Author(s)
      楢原哲史、渡邊丈久、田中健太郎、徳永尭之、川崎剛、吉丸洋子、立山雅邦、田中基彦、佐々木裕.
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Early Prediction of Sorafenib Response in Patients with Hepatocellular Carcinoma: The Possible Role of Secretory Clusterin in Acquired Sorafenib Resistance.2018

    • Author(s)
      Narahara Satoshi, Watanabe Takehisa, Nagaoka Katsuya, Fujimoto Nahoko, Tanaka Kentaro, Tokunaga Takayuki, Kawasaki Takeshi, Yoshimaru Youko, Setoyama Hiroko, Tateyama Masakuni, Naoe Hideaki, Tanaka Motohiko, Sasaki Yutaka.
    • Organizer
      The Liver Meeting (AASLD) 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2018-04-23   Modified: 2024-12-25  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi