ETS transcription factors induced by EBV in gastric epithelial cells regulate viral miRNA expression

• Project/Area Number: 18K07147
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Shimane University
• Principal Investigator: IIZASA Hisashi 島根大学, 学術研究院医学・看護学系, 准教授 (80306662)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: EBウイルス / マイクロRNA / 胃がん / 上咽頭がん / 転写因子 / 抗ウイルス薬 / EBV / miRNA / 転写 / ETS / 胃癌

Outline of Final Research Achievements

EB virus (EBV) is the causative virus of EBV-associated gastric cancer and nasopharyngeal cancer (NPC). Viral microRNAs (BART miRNAs) are highly expressed in EBV infected epithelial tumors and are involved in tumorigenesis by inhibiting apoptosis. In EBV-positive epithelial cells, expression of host transcription factors was induced, which induced expression of BART miRNAs through activation of the viral promoter. Inhibitor of this transcription factor was highly sensitive to EBV-infected cells. In addition, a single nucleotide polymorphism on the BART promoter was found to be highly correlated with NPC. These results will lead to the development of molecularly targeted drugs against EBV-infected cells, and some of the research results have been submitted for publication.

Academic Significance and Societal Importance of the Research Achievements

新型コロナウイルス感染症の流行に伴い、抗ウイルス薬の開発が大きな注目を集めている。本研究成果は、EBウイルス感染細胞を標的とした薬の開発につながる基礎研究である。また、研究過程で開発した内視鏡生検からのEBV検出法は、患者への負担がなく１回の検査で複数の感染症の有無を解析することができる。