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Seeking a novel therapy for hereditary breast cancer by modulating alternative splicing

Research Project

Project/Area Number 15K10050
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionFukuoka University (2016-2017)
Kyoto University (2015)

Principal Investigator

Ohe Kenji  福岡大学, 薬学部, 准教授 (30419527)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsスプライシング / 遺伝性乳癌
Outline of Final Research Achievements

Hereditary breast cancer caused by the BRCA1 mutation 5382insC is due to a one base pair insertion in exon 20 and results in a frame shift. In order to correct this, we tried various ways to skip exon 20, eventually which corrects the frameshift.We tried small splice modifying compounds,antisense RNA, modified U1 snRNA, and modified U7 snRMA, but all ended up in a failure. However, when we evaluated BRCA1 protein (C term Ab)by Western blot, we found TG003 increased the corrected in-frame BRCA1 protein accompanying decreased cell viability of HCC1937 cells which harbor the BRCA1 5382insC mutation endogenously.Exon skipping may have been induced in other exons besides exon 20 by TG003, which we are still persuing.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (11 results)

All 2017 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Book (2 results)

  • [Journal Article] Development of an orally available inhibitor of CLK1 for skipping a mutated dystrophin exon in Duchenne muscular dystrophy2017

    • Author(s)
      Sako Yukiya、Ninomiya Kensuke、Okuno Yukiko、Toyomoto Masayasu、Nishida Atsushi、Koike Yuka、Ohe Kenji、Kii Isao、Yoshida Suguru、Hashimoto Naohiro、Hosoya Takamitsu、Matsuo Masafumi、Hagiwara Masatoshi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 46126-46126

    • DOI

      10.1038/srep46126

    • NAID

      120006355767

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RBM24 promotes U1 snRNP recognition of the mutated 5′ splice site in the IKBKAP gene of familial dysautonomia2017

    • Author(s)
      Ohe Kenji、Yoshida Mayumi、Nakano-Kobayashi Akiko、Hosokawa Motoyasu、Sako Yukiya、Sakuma Maki、Okuno Yukiko、Usui Tomomi、Ninomiya Kensuke、Nojima Takayuki、Kataoka Naoyuki、Hagiwara Masatoshi
    • Journal Title

      RNA

      Volume: 23 Issue: 9 Pages: 1393-1403

    • DOI

      10.1261/rna.059428.116

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms2017

    • Author(s)
      Nazim M, Masuda A, Rahman MA, Nasrin F, Takeda JI, Ohe K, Ohkawara B, Ito M, Ohno K.
    • Journal Title

      Nucleic Acids Res

      Volume: - Pages: 1455-1468

    • DOI

      10.1093/nar/gkw823

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Modulation of alternative splicing with chemical compounds in new therapeutics for human diseases.2015

    • Author(s)
      Ohe K, Hagiwara M.
    • Journal Title

      ACS chemical biology

      Volume: 10 Issue: 4 Pages: 914-924

    • DOI

      10.1021/cb500697f

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] CHCHD2 mutations in autosomal dominant late-onset Parkinson’s disease: a genome-wide linkage and sequencing study.2015

    • Author(s)
      Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Yuanzhe L, Ogaki K, Ando M, Yoshinon H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N.
    • Journal Title

      Lancet Neurol

      Volume: 14 Issue: 3 Pages: 274-282

    • DOI

      10.1016/s1474-4422(14)70266-2

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia.2015

    • Author(s)
      Yoshida M, Kataoka N, Miyauchi K, Ohe K, Iida K, Yoshida S, Nojima T, Okuno Y, Onogi H, Usui T, Takeuchi A, Hosoya T, Suzuki T, Hagiwara M.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 112(9) Issue: 9 Pages: 2764-2769

    • DOI

      10.1073/pnas.1415525112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] HMGA1aに対する「おとり」RNAは、エストロゲン受容体の選択的スプライシングを制御する2016

    • Author(s)
      大江賢治,内海俊明,前田明,遠城寺宗近
    • Organizer
      第2回核酸医薬学会
    • Place of Presentation
      東京理科大学葛飾キャンパス
    • Year and Date
      2016-11-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of RNA-binding proteins responsible for aberrant tissue-specific splicing of the IKBKAP gene in Familial dysautonomia2015

    • Author(s)
      Kenji Ohe, Mayumi Yoshida, Akiko Nakano-Kobayashi, Kensuke Ninomiya, Maki Sakuma, Tomomi Usui, Takayuki Nojima, Naoyuki Kataoka, Masatoshi Hagiwara
    • Organizer
      EUKARYOTIC mRNA PROCESSING meeting 2015, Cold Spring Harbor Laboratory
    • Place of Presentation
      New York, USA
    • Year and Date
      2015-08-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of RNA-binding proteins responsible for aberrant tissue-specific splicing of the IKBKAP gene in Familial dysautonomia2015

    • Author(s)
      Kenji Ohe, Mayumi Yoshida, Akiko Nakano-Kobayashi, Kensuke Ninomiya, Maki Sakuma, Tomomi Usui, Takayuki Nojima, Naoyuki Kataoka, Masatoshi Hagiwara
    • Organizer
      第17 回日本RNA 学会年会
    • Place of Presentation
      札幌市、北海道
    • Year and Date
      2015-07-15
    • Related Report
      2015 Research-status Report
  • [Book] 選択的スプライシング・ネットワークを化合物で操作する 生体の科学 特集「細胞を化学で観察する・操作する」2015

    • Author(s)
      大江賢治、萩原正敏
    • Total Pages
      5
    • Publisher
      金原一郎医学医療振興財団
    • Related Report
      2015 Research-status Report
  • [Book] スプライシング 生体の科学 特集 細胞シグナル操作法 II. 機能からみたシグナル操作法2015

    • Author(s)
      大江賢治、飯田慶、萩原正敏
    • Total Pages
      2
    • Publisher
      金原一郎医学医療振興財団
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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