Study on DNA editing enzymes leading EB virus infected epithelial cells to tumorigenesis

• Project/Area Number: 15K19113
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Shimane University
• Principal Investigator: Kanehiro Yuichi 島根大学, 医学部, 助教 (60609197)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: EBウイルス / 上皮性腫瘍 / APOBEC / ミトコンドリア / EBV / Gastric carcinoma / Mitochondria / mitchondria DNA

Outline of Final Research Achievements

The oncogenic contribution of EBV for gastric cancer and nasopharyngeal carcinoma is not fully elucidated. In this study, we focused on DNA-editing enzyme APOBEC and clarified that EBV-induced APOBEC3 damages mitochondrial DNA via C-to-T mutagenesis. Because mitochondrial DNA damage is found in many cancers and correlates with the prognosis of cancer patients, clarifying the molecular mechanism of APOBEC3 and mitochondrial DNA damage contributes to elucidation of tumorigenesis of EBV-infected epithelial cells and leads to the development of therapeutic drugs.

Research Products

• [Journal Article] EBウイルス感染症（特集：古くて新しい日和見感染症） (2017)
  • Author(s): 金廣優一、Ricardo Timmy、Kim Hyoji、飯笹久、吉山裕規
  • Journal Title: 臨床と微生物 Volume: 44 Pages: 69-76
• [Journal Article] 感染に伴って起こるがん: Epstein-Barrウイルス関連胃癌を中心に (2016)
  • Author(s): 吉山裕規、金廣優一、Kim Hyoji、Muhtar Amrizal、Ricardo Timmy、飯笹久
  • Journal Title: 島根医学 Volume: 36 Pages: 1-6
  • Peer Reviewed / Open Access
• [Journal Article] Dysbiotic infection in the stomach. (2015)
  • Author(s): Iizasa H, Ishihara S, Richardo T, Kanehiro Y, Yoshiyama H.
  • Journal Title: Word J Gastroenterol Volume: 21 Issue: 40 Pages: 11450-11457
  • DOI: 10.3748/wjg.v21.i40.11450
  • Peer Reviewed / Open Access
• [Presentation] ルシフェラーゼアッセイを利用したPknGキナーゼに対する新規マイコバクテリア阻害剤の同定 (2017)
  • Author(s): Yuichi Kanehiro, Haruaki Tomioka, Yutaka Tatano, Timmy Richardo, Hyoji Kim, Jean Pieters, Hisashi Iizasa, and Hironori Yoshiyama
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 宮城、仙台国際センター
  • Year and Date: 2017-03-19
• [Presentation] Mitochondrial DNA mutation by APOBEC3 in EBV infected gastric epithelial cells (2016)
  • Author(s): Yuichi Kanehiro, Timmy Richardo, Hisashi Iizasa, Kim Hyoji, Masamichi Muramatsu, Hironori Yoshiyama
  • Organizer: 第64回日本ウイルス学会総会
  • Place of Presentation: 北海道、札幌コンベンションセンター
  • Year and Date: 2016-10-23
• [Presentation] EBV infection induces APOBEC3-dependent mitochondrial DNA mutation in epithelial cells (2016)
  • Author(s): Kanehiro Y, Richardo T, Kim H, Iizasa H, Yoshiyama H
  • Organizer: 17th International Symposium on EBV and associated diseases
  • Place of Presentation: Zurich, Switzerland
  • Year and Date: 2016-08-09
  • Int'l Joint Research
• [Presentation] EBV 感染は胃上皮細胞においてミトコンドリア DNA に変異を誘導する (2016)
  • Author(s): Timmy Richardo、金廣優一、Hyoji Kim、飯笹久、吉山裕規
  • Organizer: 第31回中国四国ウイルス研究会
  • Place of Presentation: 鳥取、鳥取大学農学部大講義室
  • Year and Date: 2016-07-09
• [Presentation] 胃上皮細胞におけるEBV感染はAPOBEC3の発現誘導を介してミトコンドリアDNAに変異を導入する (2016)
  • Author(s): 金廣 優一、Timmy Richardo 、Hyoji Kim、飯笹 久、吉山 裕規
  • Organizer: 第30回ヘルペスウイルス研究会
  • Place of Presentation: 東京、セミナーハウスクロス・ウェーブ府中
  • Year and Date: 2016-06-16
• [Presentation] Evalution of genetic instability of cells infected with Epstain-Barr virus (2015)
  • Author(s): Hyoji Ki、飯笹久、金廣優一、Timmy Richardo、吉山裕規
  • Organizer: 第６３回日本ウイルス学会学術集会
  • Place of Presentation: 福岡（福岡国際会議場）
  • Year and Date: 2015-11-22
• [Presentation] EBV感染に伴う細胞ゲノム不安定性について (2015)
  • Author(s): Timmy Richardo、飯笹久、金廣優一、吉山裕規
  • Organizer: 第１２回EBウイルス研究会
  • Place of Presentation: 島根（ビッグハート出雲）
  • Year and Date: 2015-07-20
• [Book] EBウイルス関連胃癌 (2016)
  • Author(s): 金廣優一、Ricardo Timmy、飯笹 久、吉山裕規
  • Total Pages: 92
  • Publisher: 診断と治療社