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Elucidation of functional significance of ZNF395 downregulation and development of novel therapeutic strategy for pancreatic ductal adenocarcinoma.

Research Project

Project/Area Number 21K20779
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0803:Pathology, infection/immunology, and related fields
Research InstitutionOita University

Principal Investigator

Kurogi Shusaku  大分大学, 医学部, 技術専門職員 (50905213)

Project Period (FY) 2021-08-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsZNF395 / 膵癌 / 細胞周期 / ストレス応答MAPキナーゼ
Outline of Research at the Start

膵癌は、前癌病変→上皮内癌→浸潤癌へと段階的に進展すると考えられているが、上皮内癌が浸潤癌に進展する際に付加される遺伝子異常やそのメカニズムはまだ十分に解明されていない。私は、膵上皮内癌が浸潤癌へ進展する過程で、8番染色体短腕の欠失に伴いZincfinger protein 395 (ZNF395)の発現低下が生じること、それにより膵癌細胞は増殖能を獲得することを見出した。さらに、ZNF395の発現低下が細胞周期の脱制御をもたらすことを明らかにした。本研究は、膵癌の新規がん抑制遺伝子ZNF395の機能的意義を詳細に解明して、新規治療法の確立を目指すものである。

Outline of Final Research Achievements

In our previous studies, we found that Downregulation of ZNF395 enhances cell proliferative potential and contributes to the progression of pancreatic intraepithelial neoplasia to invasive carcinoma. In the present study, we attempted to identify the signaling pathways associated with ZNF395 by comprehensive gene expression analysis to elucidate the functional significance of ZNF395. As a result, four genes (NDRG1, ARMCX6, DDIT4 and ERCC5) were identified whose expression levels were associated with ZNF395. We currently analyze the association between these genes and ZNF395 and investigate their potential as a new therapeutic strategy for pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

膵癌は5年生存率が10%未満であり、最も予後不良な癌腫である。この極めて厳しい現状を打破するためには、今までにない革新的な治療法の開発が求められる。本研究では、膵癌の進展に関わる新規がん抑制遺伝子として見出したZNF395に着目し、ZNF395に関連しているがん抑制遺伝子候補を4遺伝子同定した。これらの遺伝子の中には、膵癌の浸潤、増殖、血管新生を抑制すると報告されている遺伝子もあり、新たな治療戦略の開発に重要な知見をもたらすと考えられる。本研究が発展すれば、膵癌の治療成績を改善することが期待でき、その社会的意義は極めて大きいといえる。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (5 results)

All 2023 2022 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (1 results)

  • [Journal Article] Involvement of clusterin expression in the refractory response of pancreatic cancer cells to a MEK inhibitor.2023

    • Author(s)
      Amada K, Hijiya N, Ikarimoto S, Yanagihara K, Hanada T, Hidano S, Kurogi S, Tsukamoto Y, Nakada C, Kinoshita K, Hirashita Y, Uchida T, Shin T, Yada K, Hirashita T, Kobayashi T, Murakami K, Inomata M, Shirao K, Aoki M, Takekawa M, Moriyama M.
    • Journal Title

      Cancer Sci.

      Volume: 114 Issue: 5 Pages: 2189-2202

    • DOI

      10.1111/cas.15735

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficient Establishment of Bile-Derived Organoids From Patients With Biliary Cancer.2023

    • Author(s)
      Kinoshita K, Tsukamoto Y, Hirashita Y, Fuchino T, Kurogi S, Uchida T, Nakada C, Matsumoto T, Okamoto K, Motomura M, Fukuchi S, Sagami R, Nagai T, Gotoh Y, Fukuda K, Ogawa R, Mizukami K, Okimoto T, Kodama M, Murakami K, Moriyama M, Hijiya N.
    • Journal Title

      Lab Invest.

      Volume: 103 Issue: 6 Pages: 100105-100105

    • DOI

      10.1016/j.labinv.2023.100105

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced phosphorylation of c-Jun by cisplatin treatment as a potential predictive biomarker for cisplatin response in combination with patient-derived tumor organoids.2022

    • Author(s)
      Tsukamoto Y, Kurogi S, Shibata T, Suzuki K, Hirashita Y, Fumoto S, Yano S, Yanagihara K, Nakada C, Mieno F, Kinoshita K, Fuchino T, Mizukami K, Ueda Y, Etoh T, Uchida T, Hanada T, Takekawa M, Daa T, Shirao K, Hironaka S, Murakami K, Inomata M, Hijiya N, Moriyama M.
    • Journal Title

      Lab Invest.

      Volume: 102 (12) Issue: 12 Pages: 1355-1366

    • DOI

      10.1038/s41374-022-00827-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Downregulation of ZNF395 Drives Progression of Pancreatic Ductal Adenocarcinoma through Enhancement of Growth Potential.2021

    • Author(s)
      Kurogi S, Hijiya N, Hidano S, Sato S, Uchida T, Tsukamoto Y, Nakada C, Yada K, Hirashita T, Inomata M, Murakami K, Takahashi N, Kobayashi T, Moriyama M.
    • Journal Title

      Pathobiology

      Volume: 2021 Issue: 5 Pages: 1-9

    • DOI

      10.1159/000514593

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ZNF395の発現低下はJNKの不活性化を介して膵癌細胞の増殖を促進する2021

    • Author(s)
      黒木 秀作, 泥谷 直樹, 塚本 善之, 中田 知里, 猪股 雅史, 小林 隆志, 守山 正胤
    • Organizer
      第80回 日本癌学会学術総会
    • Related Report
      2021 Research-status Report

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Published: 2021-10-22   Modified: 2024-01-30  

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