• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of mRNA splicing modulators to overcome anticancer drug resistance

Research Project

Project/Area Number 21K07202
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionFujita Health University

Principal Investigator

Fukumura Kazuhiro  藤田医科大学, 医科学研究センター, 講師 (80622117)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsRNAスプライシング / SPF45 / 抗がん剤耐性 / 異常mRNAスプライシング / 抗がん剤耐性獲得 / SAP30BP / mRNA前駆体スプライシング / mRNAスプライシング / ペプチド医薬
Outline of Research at the Start

抗がん剤治療において、抗がん剤耐性獲得のメカニズムは未解明な点が多い。SPF45は、ショウジョウバエにおいてmRNAスプライシング制御因子として同定されているが、ヒトでは抗ガン剤耐性遺伝子として様々ながん組織で過剰発現が報告されている。しかし、その作用機序は不明である。本研究は、申請者の基礎研究を発展させ、スプライシング制御因子SPF45の過剰発現による抗がん剤耐性獲得メカニズムを解明、応用研究によって新規抗がん剤の創出を目指す。

Outline of Final Research Achievements

The human SPF45 gene has been reported to be overexpressed in cancer cells, conferring resistance to anticancer drugs. However, the mechanism of this phenomenon has not been elucidated. In this study, I showed that SPF45 is a novel regulator essential for mRNA splicing of very short introns in human genes and published their results in two international journals [Fukumura et al. Nat. Commun. 12, 4910 (2021)] et al. Cell Rep. 42, 113534 (2023)]. In cancer cells, overexpression of SPF45 is thought to cause abnormal mRNA splicing.

Academic Significance and Societal Importance of the Research Achievements

研究代表者の研究成果から、SPF45過剰発現による抗がん剤耐性獲得機構の一端を理解することができた。これまで、スプライシング制御因子の異常に着目した抗がん剤耐性の獲得機構という研究は前例がなく新しい取り組みと言えるであろう。本研究成果により、抗がん剤耐性獲得メカニズムの研究において新しい領域を開拓できたのではないかと考える。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (11 results)

All 2023 2022 2021

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] SAP30BP interacts with RBM17/SPF45 to promote splicing in a subset of human short introns2023

    • Author(s)
      Fukumura Kazuhiro、Sperotto Luca、Seu? Stefanie、Kang Hyun-Seo、Yoshimoto Rei、Sattler Michael、Mayeda Akila
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 12 Pages: 113534-113534

    • DOI

      10.1016/j.celrep.2023.113534

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RBM17 expression Is associated with the efficacy of ICI monotherapy in NSCLC with low PD-L1 expression.2023

    • Author(s)
      H. Nagamine, M. Yashiro, N. Yoshimoto, M. Izumi, A. Sugimoto, K. Nakahama, K. Ogawa, Y. Matsumoto, K. Sawa, Y. Tani, H. Kaneda, S. Mitsuoka, K. Yamada, T. Watanabe, K. Aasai, K. Fukumura, A. Mayeda, T. Kawaguchi
    • Journal Title

      Anticancer Research

      Volume: 43 Issue: 10 Pages: 4663-4672

    • DOI

      10.21873/anticanres.16662

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The mysteries of ‘intron length’ triggered the discovery of novel mechanisms of splicing2022

    • Author(s)
      福村 和宏、前田 明
    • Journal Title

      生化学

      Volume: 94 Issue: 6 Pages: 806-813

    • DOI

      10.14952/SEIKAGAKU.2022.940806

    • ISSN
      0037-1017
    • Year and Date
      2022-12-25
    • Related Report
      2022 Research-status Report
  • [Journal Article] Novel LAMC2 fusion protein has tumor‐promoting properties in ovarian carcinoma2021

    • Author(s)
      Daisuke Hoshino、Kato Hisamori、Fukumura Kazuhiro、Mayeda Akila、Miyagi Yohei、Seiki Motoharu、Koshikawa Naohiko
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 12 Pages: 4957-4967

    • DOI

      10.1111/cas.15149

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SPF45/RBM17-dependent, but not U2AF-dependent, splicing in a distinct subset of human short introns2021

    • Author(s)
      Fukumura Kazuhiro、Yoshimoto Rei、Sperotto Luca、Kang Hyun-Seo、Hirose Tetsuro、Inoue Kunio、Sattler Michael、Mayeda Akila
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41467-021-24879-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SPF45/RBM17-dependent splicing implicated in multidrug resistance in cancer chemotherapy.2021

    • Author(s)
      K. Fukumura, J.P. Venables, A. Mayeda
    • Journal Title

      Mol. Cell. Oncol.

      Volume: 8 Issue: 6 Pages: 1996318-1996318

    • DOI

      10.1080/23723556.2021.1996318

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] SAP30BP-RBM17 interaction is an essential process to splice out a subset of human short introns2023

    • Author(s)
      福村和宏
    • Organizer
      第46回日本分子生物学会年
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] RNPS1 in PSAP complex controls precise pre-mRNA splicing with periodicity during cell cycle2022

    • Author(s)
      Fukumura K., Takeda J., Masuda A., Ohno M. & Mayeda A.
    • Organizer
      第 23 回日本 RNA 学会年会(2022)
    • Related Report
      2022 Research-status Report
  • [Presentation] RNPS1 in PSAP Complex Controls Pre-mRNA splicing with Periodicity during Cell Cycle2022

    • Author(s)
      Fukumura K. & Mayeda A.
    • Organizer
      Gordon Research Conference PostTranscriptional Gene Regulation&Integrating (2022)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新しい分子機構によってスプライシングされるヒトの短いイントロン群2021

    • Author(s)
      Kazuhiro Fukumura, Rei Yoshimoto, Tetsuro Hirose, Kunio Inoue , Akila Mayeda
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Book] mRNAの制御機構の解明と治療薬・ワクチンへの活用2023

    • Author(s)
      執筆者:73名、技術情報協会
    • Total Pages
      411
    • Publisher
      技術情報協会
    • ISBN
      9784861049378
    • Related Report
      2022 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi