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Investigation of the global effect and the mechanism of cancer specific mature mRNA re-splicing

Research Project

Project/Area Number 26430124
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionFujita Health University

Principal Investigator

Kameyama Toshiki  藤田保健衛生大学, 総合医科学研究所, 助教 (60298544)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsがん / 異常スプライシング / RNA結合タンパク質 / siRNAライブラリー / siRNA / RBM4 / シスプラチン / mRNA再スプライシング / p53 / RNase R / 成熟mRNA再スプライシング / 次世代シークエンス
Outline of Final Research Achievements

We have discovered cancer-specific mRNA re-splicing that occurs on mature spliced mRNA and generates aberrant transcripts/proteins. The control of the re-splicing could be promoted by unknown activator upregulated and/or repressor downregulated in cancer cells.
Recent striking findings represent a breakthrough in the study of mRNA re-splicing. (1) TSG101 delta protein, generated via re-splicing of TSG101, enhances TSG101-stimulated cell proliferation and tumor growth. (2) mRNA re-splicing is repressed by the expression of TP53 often induced by cellular stress, (3) We have identified a repressor candidate of mRNA re-splicing by screening of siRNA library (156 kinds of RNA-binding proteins). Since the identified repressor is a known tumor suppressor, we postulate that global prevention of aberrant mRNA re-splicing, maintaining fidelity of splicing, is critical for the consequent tumor suppression. To prove this hypothesis is underway.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (23 results)

All 2017 2016 2015 2014 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Remarks (4 results)

  • [Journal Article] Endogenous Multiple Exon Skipping and Back-Splicing at the DMD Mutation Hotspot2016

    • Author(s)
      Hitoshi Suzuki, Yoshitsugu Aoki, Toshiki Kameyama, Takashi Saito, Satoru Masuda, Jun Tanihata, Tetsuya Nagata, Akila Mayeda, Shin’ichi Takeda, Toshifumi Tsukahara
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 17 Issue: 10 Pages: 1722-1722

    • DOI

      10.3390/ijms17101722

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transcriptional activation of platelet-derived growth factor receptor α and GS homeobox 2 resulting from E26 transformation-specific variant 6 translocation in a case of acute myeloid leukemia with t(4;12)(q12;p13).2016

    • Author(s)
      Abe A, Mizuta S, Okamoto A, Yamamoto Y, Kameyama T, Mayeda A, Emi N.
    • Journal Title

      International journal of laboratory hematology

      Volume: 38(2) Issue: 2 Pages: 15-18

    • DOI

      10.1111/ijlh.12450

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] ETV6-LPXN fusion transcript generated by t(11;12)(q12.1;p13) in a patient with relapsing acute myeloid leukemia with NUP98-HOXA9.2016

    • Author(s)
      Abe A, Yamamoto Y, Iba S, Kanie T, Okamoto A, Tokuda M, Inaguma Y, Yanada M, Morishima S, Mizuta S, Akatsuka Y, Okamoto M, Kameyama T, Mayeda A, Emi N.
    • Journal Title

      Genes, chromosomes & cancer

      Volume: 55(3) Issue: 3 Pages: 242-250

    • DOI

      10.1002/gcc.22327

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] NUP214-RAC1 and RAC1-COL12A1 Fusion in Complex Variant Translocations Involving Chromosomes 6, 7 and 9 in an Acute Myeloid Leukemia Case with DEK-NUP214.2015

    • Author(s)
      Abe A, Yamamoto Y, Iba S, Okamoto A, Tokuda M, Inaguma Y, Yanada M, Morishima S, Kanie T, Tsuzuki M, Akatsuka Y, Mizuta S, Okamoto M, Kameyama T, Mayeda A, Emi N.
    • Journal Title

      Cytogenetic and genome research

      Volume: 146(4) Issue: 4 Pages: 279-284

    • DOI

      10.1159/000441464

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] がん細胞で異常なタンパク質が作られるしくみを「mRNA再スプライシング」現象から探る2015

    • Author(s)
      亀山俊樹、前田明
    • Journal Title

      ファルマシア

      Volume: 51 Pages: 22-26

    • Related Report
      2014 Research-status Report
  • [Journal Article] Fluvoxamine moderates reduced voluntary activity following chronic dexamethasone infusion in mice via recovery of BDNF signal cascades.2014

    • Author(s)
      Terada K, *Izumo N, Suzuki B, Karube Y, Morikawa T, Ishibashi Y, Kameyama T, Chiba K, Sasaki N, Iwatae K, Matsuzaki H. and *Manabe T.
    • Journal Title

      Neurochem. Int.

      Volume: 69 Pages: 9-13

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spatiotemporal expression pattern of Myt/NZF family zinc finger transcription factors during mouse nervous system development.2014

    • Author(s)
      Fumio Matsushita, *Toshiki Kameyama, Yuzo Kadokawa and Tohru Marunouchi
    • Journal Title

      Developmental Dynamics.

      Volume: 243 Issue: 4 Pages: 588-600

    • DOI

      10.1002/dvdy.24091

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] A Repressor Candidate of Cancer Specific mRNA Re-splicing: A Key factor for splicing fidelity or mRNA quality control?2017

    • Author(s)
      Toshiki Kameyama, Kazuhiro Fukumura, Kunio Inoue, Tetsuro Hirose, Akila Mayeda
    • Organizer
      RNA2017 The 22nd Annual Meeting of the RNA Society
    • Place of Presentation
      Prague Congress Center, Prague, Czech Republic
    • Year and Date
      2017-05-30
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Repressor Candidate of Cancer Specific mRNA Re-splicing: A Key factor for splicing fidelity or mRNA quality control?2017

    • Author(s)
      Toshiki Kameyama, Kazuhiro Fukumura, Kunio Inoue, Tetsuro Hirose, Akila Mayeda
    • Organizer
      International Symposium on the Hallmarks of Cancer: Focus on RNA
    • Place of Presentation
      Institute of Molecular Genetics of the ASCR, v. v. i. Prague, Czech Republic
    • Year and Date
      2017-05-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cisplatin-stimulated Cancer-specific Mature mRNA Re-splicing Is under the Control of Tumor Suppressor p53.2016

    • Author(s)
      Toshiki Kameyama, Yoshinosuke Amemoto, Akila Mayeda
    • Organizer
      The 21th Annual Meeting of the RNA Society/The 18th Annual Meeting of the RNA Society of Japan
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2016-06-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] t(8;12;21)(q22:p12;q22)を有するRUNX1-RUNX1T1白血病に認められたTM7SF4-VPS13B融合遺伝子2015

    • Author(s)
      安部明弘、山本幸也、岡本晃直、徳田倍将、稲熊容子、山本起代子、柳田正光、森島聡子、蟹江匡治、赤塚美樹、水田秀一、岡本昌隆、亀山俊樹、前田  明、恵美宣彦
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      石川県立音楽堂(石川県金沢市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Hypoxia had an effect on cancer-specific mature mRNA re-splicing.2015

    • Author(s)
      Toshiki Kameyama, Shota Matsumiya and Akila Mayeda.
    • Organizer
      Cold Spring Harbor Laboratory Meeting “ Eukaryotic mRNA Processing”
    • Place of Presentation
      Cold Spring Harbor Laboratory, NY USA
    • Year and Date
      2015-08-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 低酸素ストレスは癌細胞特異的成熟mRNA再スプライシングに影響を与える2015

    • Author(s)
      亀山俊樹、松宮翔太、前田明
    • Organizer
      第17回日本RNA学会年会
    • Place of Presentation
      ホテルライフォート札幌(北海道札幌市)
    • Year and Date
      2015-07-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Mature mRNA Re-splicing in Cancer Cells2015

    • Author(s)
      Toshiki Kameyama
    • Organizer
      Invited Seminar for Harvard Medical School
    • Place of Presentation
      Beth Israel Deaconess Medical Center
    • Year and Date
      2015-02-05
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Novel cancer specific mature mRNA re-splicing postulates undiscovered mRNA quality control mechanism in normal cells.2015

    • Author(s)
      Toshiki Kameyama and Akila Mayeda
    • Organizer
      The 10th Cold Spring Harbor Conference “Systems Biology: Global Regulation of Gene Expression”
    • Place of Presentation
      The Wyndham Grand Rio Mar, Puerto Rico
    • Year and Date
      2015-01-28 – 2015-02-01
    • Related Report
      2014 Research-status Report
  • [Presentation] Additional NUP214-RAC1 fusion gene in an AML patient with DEK-NUP2142014

    • Author(s)
      安部明弘、山本幸也、岡本晃直、徳田倍将、稲熊容子、柳田正光、森島聡子、蟹江匡治、都築基弘、赤塚美樹、水田秀一、岡本昌隆、亀山俊樹、前田 明、恵美宣彦
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪 大阪国際会議場
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Novel mRNA re-splicing event: important aspects for understanding robustness and catastrophe in gene expression systems.2014

    • Author(s)
      Toshiki Kameyama and Akila Mayeda
    • Organizer
      RIKEN Symposium & The 15th Tokyo RNA Club “Noncoding RNA Regulation”
    • Place of Presentation
      Suzuki Umetaro Hall, RIKEN, Wako, Saitama
    • Year and Date
      2014-10-01
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] がん細胞での成熟mRNA再スプライシング活性に影響を与える核外輸送因子2014

    • Author(s)
      亀山 俊樹、増田 誠司、前田 明
    • Organizer
      RNA2014 第16回日本RNA学会年会
    • Place of Presentation
      名古屋 WINC AICHI
    • Year and Date
      2014-07-23 – 2014-07-25
    • Related Report
      2014 Research-status Report
  • [Presentation] 長鎖ノンコーディングRNA Malat1におけるスプライシング抑制機構の存在2014

    • Author(s)
      佐々木(原口) 典子、亀山 俊樹、眞部 孝幸、秋光 信佳、前田 明
    • Organizer
      RNA2014 第16回日本RNA学会年会
    • Place of Presentation
      名古屋 WINC AICHI
    • Year and Date
      2014-07-23 – 2014-07-25
    • Related Report
      2014 Research-status Report
  • [Remarks] 藤田保健衛生大学 総合医科学研究所 遺伝子発現機構学研究部門

    • URL

      http://www.fujita-hu.ac.jp/~gem-1/

    • Related Report
      2015 Research-status Report
  • [Remarks] 藤田保健衛生大学総合医科学研究所遺伝子発現機構学研究部門ホームページ

    • URL

      http://www.fujita-hu.ac.jp/~gem-1/

    • Related Report
      2014 Research-status Report
  • [Remarks] 新学術領域研究 がん研究分野の特性等を踏まえた支援活動:研究者海外派遣事業レポート

    • URL

      http://ganshien.umin.jp/about/sogo/kokusai/report/20150128.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 新学術領域研究 がん研究分野の特性等を踏まえた支援活動:研究紹介

    • URL

      http://ganshien.umin.jp/research/spotlight/maeda/

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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