Mechanisms of EBV-mediated gastric carcinogenesis through the exosome-induced signaling.

• Project/Area Number: 26460932
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Human Arts and Sciences (2016); Kobe University (2015); Hokkaido University (2014)
• Principal Investigator: Iwakiri Dai 人間総合科学大学, 人間科学部, 特任教授 (10307853)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: EBウイルス / 胃がん / EBER / TLR3 / EBV / エクソソーム / 自然免疫

Outline of Final Research Achievements

We demonstrated that EBV-encoded small RNA (EBER) is released by EBV-infected gastric cancer (GC) cells through the exosome secretion and exosomal transfer of EBER triggers the signaling from toll-like receptor 3 in the recipient cells. EBER-mediated activation of TLR3 signals led to the growth promotion of EBV-infected gastric cancer cells, suggesting that exosomal transfer of EBER contributes to gastric carcinogenesis. Further study revealed that treatment with exosome inhibitor reduces the growth potential of EBV-infected GC cells.

Research Products

• [Journal Article] Evaluation of the risk of lymphomagenesis in xenografts by the PCR-based detection of EBV BamHI W region in patient cancer specimens. (2016)
  • Author(s): Mukohyama J, Iwakiri, D, Zen Y, Mukohara T, Minami H, Kakeji Y, Shimono Y.
  • Journal Title: Oncotarget Volume: 31 Issue: 31 Pages: 50150-50160
  • DOI: 10.18632/oncotarget.10322
  • NAID: 120005890089
  • Peer Reviewed / Open Access
• [Journal Article] Multifunctional non-coding Epstein-Barr virus encoded RNAs (EBERs) contribute to viral pathogenesis. (2015)
  • Author(s): Iwakiri D
  • Journal Title: VIrus Research Volume: 15 Pages: 30039-3
  • DOI: 10.1016/j.virusres.2015.08.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] EBウイルスによる発癌機構 (2015)
  • Author(s): 岩切 大
  • Journal Title: 癌と化学療法 Volume: 42 Pages: 1133-1136
  • NAID: 10018452069
• [Journal Article] Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis (2014)
  • Author(s): Iwakiri D
  • Journal Title: Cancers Volume: 6 Issue: 3 Pages: 1615-1630
  • DOI: 10.3390/cancers6031615
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Molecular Mechanisms of Epstein-Barr virus-mediated carcinogeneis (2014)
  • Author(s): 岩切 大
  • Journal Title: Uirusu Volume: 64 Issue: 1 Pages: 49-56
  • DOI: 10.2222/jsv.64.49
  • NAID: 130004922978
  • ISSN: 0042-6857, 1884-3433
• [Journal Article] EB ウイルス感染と胃発癌 (2014)
  • Author(s): 岩切 大
  • Journal Title: 日本臨床 Volume: 増刊 Pages: 58-62
• [Presentation] Molecular mechanisms of Epstein-Barr virus-mediated oncogenesis. (2015)
  • Author(s): Iwakiri D.
  • Organizer: Seminar in University of Rome
  • Place of Presentation: University of Rome
  • Year and Date: 2015-07-01
  • Invited
• [Presentation] 胃癌細胞におけるEBウイルス小RNAノexosome輸送を介した機能発現 (2014)
  • Author(s): 岩切 大
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Activation of toll-like receptor 3 signaling by EBV-encoded small RNA contributes to gastric carcinogenesis (2014)
  • Author(s): Iwakiri D.
  • Organizer: 17th Annual meeting of European society for clinical virology
  • Place of Presentation: プラハ (チェコ)
  • Year and Date: 2014-09-29 – 2014-10-02
• [Presentation] Exosomal transfer of Epstein-Barr virus-encoded small RNA contributes to gastric cancer development. (2014)
  • Author(s): iwakiri D.
  • Organizer: 39th International Herpesvirus Workshop
  • Place of Presentation: 神戸国際会議場 (兵庫県神戸市)
  • Year and Date: 2014-07-19 – 2014-07-23