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

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15820
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kumamoto 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
• Keywords: miRNA / DAAs / SVR / exosome / 癌 / 代謝異常 / HCV

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.

Free Research Field

消化器内科

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。