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Elucidation of three dimensional genome organization by Brd4 that confers cancer stemness

Research Project

Project/Area Number 17K15618
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionOsaka University

Principal Investigator

Yokoyama Yuhki  大阪大学, 医学系研究科, 助教 (60615714)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords三次元ゲノム構造 / エピジェネティクス / 大腸癌 / 癌幹細胞 / ゲノム / 癌
Outline of Final Research Achievements

We initially planned to conduct study mainly using ovarian cancer cell lines, but the study using colorectal cancer cell lines progressed smoothly. Therefore, we focused on the study for colorectal cancer. In the first year, we found that the expression of cancer stem cell related genes were suppressed by the BET family protein inhibitor JQ1 in colorectal cancer as reported in ovarian cancer. We focused on the KLF5 gene, which has been reported as one of the cancer stem cell related gene, and preceded the study. As a result of analysis by the enChIP method, the enhancer candidate regions of the KLF5 gene were identified. In the second year, in situ Hi-C experiment was performed, and we found that the enhancer regions of the KLF5 gene may be located in the same TAD (topologically associating domain) as the KLF5 gene promoter region.

Academic Significance and Societal Importance of the Research Achievements

癌幹細胞は腫瘍組織内に少数存在し、抗がん剤耐性や自己複製能、高い腫瘍形成能を持つことから、再発や転移の原因として考えられている。そのため、癌幹細胞を標的とした治療法の開発が望まれている。本研究の成果はKLF5遺伝子をはじめとした大腸癌の幹細胞関連遺伝子がBETファミリータンパクによって構築される三次元ゲノム構造を介して制御されている可能性を示すものであり、癌幹細胞を標的とした治療法の開発につながる可能性がある。

Report

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

    (3 results)

All 2019 2018

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] The identification of KLF5 enhancer region in colorectal cancer2019

    • Author(s)
      Yuhki Yokoyama, Takashi Takeda, Kumi Kitagawa, Daisuke Okuzaki, Toshitsugu Fujita, Hodaka Fujii, Hirofumi Yamamoto
    • Organizer
      KEYSTONE SYMPOSIA 3D Genome:Gene Regulation and Disease
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BET阻害剤はALDH1A1遺伝子のスーパーエンハンサーを標的として卵巣癌のALDH活性を抑制する2018

    • Author(s)
      横山雄起、武田和、北川公望、森誠司、水島恒和、森正樹、松浦成昭、山本浩文
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大腸癌細胞株におけるBET阻害剤JQ1の効果2018

    • Author(s)
      武田和、横山雄起、北川公望、三吉範克、高橋秀和、原口直紹、西田尚弘、畑泰司、松田宙、水島恒和、土岐祐一郎、森正樹、山本浩文
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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