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Oncolytic virus targeting oral cancer stem cells

Research Project

Project/Area Number 18K09737
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionHokkaido University

Principal Investigator

YASUDA MOTOAKI  北海道大学, 歯学研究院, 准教授 (90239765)

Co-Investigator(Kenkyū-buntansha) 東野 史裕  北海道大学, 歯学研究院, 准教授 (50301891)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsアデノウイルス / UTR / 口腔がん / adenovirus / tripartite leader / UTR / がん幹細胞 / 非翻訳領域
Outline of Final Research Achievements

All transcribed mRNAs, a minimum of 20 late viral RNAs, contain the common 5’UTR, which is called as Tripartite Leader, and this sequence is required for preferential translation of late viral proteins during late infection period. In the present study, we have demonstrated a novel role for E4 orf4 protein in the late adenoviral mRNA translation. Tripartite Leader tagged construct (TrLdr-LUC) transfected cells showed more than 10-fold higher luciferase activity compared with control transfectants, whereas no significant increase of luciferase mRNA amount was detected in TrLdr-LUC transfected cells. At least 2 folds increase of luciferase activities were observed, and the mutational analysis indicated that E4orf4, but not E4 orf3 or E4 orf6, was required for the enhanced translation. It is likely that E4 orf4 or OMB1 containing complex is involved in so-called Ribosome Shunt system.

Academic Significance and Societal Importance of the Research Achievements

アデノウイルスは遺伝子治療研究の約25%で使用されるベクターであるが、ほとんどの組み換えウイルスは自己複製不能で全てのがん細胞への導入は困難であり、また大量に感染させると肝臓に集積し副作用の原因となる。本研究で明らかとなったウイルス遺伝子翻訳システムの詳細は腫瘍溶解アデノウイルスをより効果的な手法とするのに有用である。また”がん幹細胞”における本翻訳システムの詳細についての解析は、さらに効果的な腫瘍会ウイルス作成への大きな一歩となる。

Report

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

    (4 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA2020

    • Author(s)
      Mikawa Yohei、Towfik Alam Mohammad、Hossain Elora、Yanagawa-Matsuda Aya、Kitamura Tetsuya、Yasuda Motoaki、Habiba Umma、Ahmed Ishraque、Kitagawa Yoshimasa、Shindoh Masanobu、Higashino Fumihiro
    • Journal Title

      Cancers

      Volume: 12 Issue: 5 Pages: 1205-1205

    • DOI

      10.3390/cancers12051205

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The neural ELAVL protein HuB enhances endogenous proto-oncogene activation.2019

    • Author(s)
      Hatanaka T, Higashino F, Tei K, Yasuda M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 517(2) Issue: 2 Pages: 38-45

    • DOI

      10.1016/j.bbrc.2019.07.089

    • NAID

      120006886034

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncolytic potential of an E4-deficient adenovirus that can recognize the stabilization of AU-rich element containing mRNA in cancer cells.2018

    • Author(s)
      Yanagawa-Matsuda A, Mikawa Y, Habiba U, Kitamura T, Yasuda M, Towfik-Alam M, Kitagawa Y, Minowa K, Shindoh M, Higashino F
    • Journal Title

      Oncol Rep.

      Volume: 41(2) Pages: 954-960

    • DOI

      10.3892/or.2018.6865

    • NAID

      120006709288

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] A novel role for E4 orf4 in the translation of late adenovirus mRNA2018

    • Author(s)
      Motoaki Yasuda, Fumihiro Higashino
    • Organizer
      RNA学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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