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Elucidation of cancer progression through dysfunction of ubiquitin system

Research Project

Project/Area Number 16K10513
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionNara Medical University

Principal Investigator

Migita Kazuhiro  奈良県立医科大学, 医学部, 研究員 (40570990)

Research Collaborator Obara Shinsaku  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords胃癌 / E3ユビキチンリガーゼ / 外科
Outline of Final Research Achievements

We investigated the roles of Ring finger protein 126 (RNF126) in the progression of gastric cancer. In the immunohistochemical analyses, the RNF126 expression level was significantly associated with the tumor depth. The patients with a RNF126-high tumor had a significantly lower overall survival rate than the patients with a RNF126-low tumor. Multivariate analysis identified the RNF126 status as an independent prognostic factor. We further investigated the roles of RNF126 in vitro using a small interfering RNA (siRNA). RNF126 gene silencing significantly inhibited the proliferation of human gastric cancer cells, MKN45 and MKN74, through the cell cycle arrest. Furthermore, RNF126 gene silencing improved the sensitivity to 5-FU. Our findings indicate that RNF126 might play an important role in regulating the proliferation and chemo-resistance of gastric cancer cells.

Academic Significance and Societal Importance of the Research Achievements

本研究はユビキチンシステムにおいて中心的役割を担うE3ユビキチンリガーゼに着目し、胃癌進展におけるその異常の意義・役割を検討した。E3ユビキチンリガーゼであるRNF126はヒト胃癌組織で過剰発現しており、その発現レベルは腫瘍進達度と関連し、独立した予後規定因子となるなど臨床的意義を有することが判明した。また、発現レベルは胃癌細胞の増殖能、抗癌剤への感受性に関連することが明らかとなり、RNF126は胃癌の増殖、治療抵抗性に深く関与することが示唆された。本研究の成果はユビキチンシステム異常を介した消化器癌進展の解明、新たな癌治療開発の礎となるものと考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2019 2018 2017

All Presentation (4 results)

  • [Presentation] High expression of RNF126 is associated with poor prognosis of gastric cancer.2019

    • Author(s)
      K. Migita, S. Matsumoto, K. Wakatsuki, T. Kunishige, H. Nakade, S. Miyao, M. Sho
    • Organizer
      第91回日本胃癌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胃癌におけるRNF126の意義2018

    • Author(s)
      右田和寛、松本壮平、若月幸平、伊藤眞廣、國重智裕、中出裕士、北野睦子、中谷充弘、庄 雅之
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Clinical significance of RNF126 in gastric cancer.2018

    • Author(s)
      K. Migita, S. Matsumoto, K. Wakatsuki, M. Ito, T. Kunishige, H. Nakade, M. Sho
    • Organizer
      第77回日本癌学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胃癌におけるRNF126発現の臨床的意義2017

    • Author(s)
      右田和寛、松本壮平、若月幸平、伊藤眞廣、國重智裕、中出裕士、北野睦子、中谷充弘、金廣裕道、庄 雅之
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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