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低分子RNAの生合成機構の多様性と病態形成での役割に関する研究

Publicly Offered Research

Project AreaDiversity and asymmetry achieved by RNA program
Project/Area Number 23112702
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

鈴木 洋  東京大学, 医学(系)研究科(研究院), 特任助教 (00587793)

Project Period (FY) 2011-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords低分子RNA / 遺伝子 / 病理学 / シグナル伝達 / 癌 / 低分子RNA
Outline of Annual Research Achievements

本研究では、マイクロRNA(miRNA)などの低分子RNAプログラムの品質管理機構の分子基盤を明らかにし、その機構の悪性腫瘍およびウイルス感染における役割を解析し、病態把握への応用の可能性を検討することを目的とする。本研究にて、MCPIP1と呼ばれる遺伝子をmiRNAによるRNAサイレンシングの負の調節因子として同定し、MCPIP1が細胞質でribonucleaseとしてmiRNA前駆体のループ部分を切断しmiRNAの生合成を終息させること、MCPIP1がmiRNAの生合成における中心的なribonucleaseであるDicerと拮抗することなどを見出し、これまで未知であったmiRNA産生を負に調節する経路を新たに発見した(Molecular Cell, 44, 424-436)。平成24年度には、MCPIP1によるmiRNA前駆体の分解を抑制するRNA結合タンパクLaとMCPIP1の関係について、乳癌の遺伝子発現データを解析し、結果として、DicerおよびLaとMCPIP1の発現量が乳癌の予後に与える影響が拮抗関係にあることを見出した(J Biol Chem, 288, 723-736)。また、癌における遺伝子発現調節ネットワークにおいて、miRNAによるネットワーク制御の意義を解明し、新規バイオマーカーや新規治療標的を見出すことを目的とし、GSEA-FAME analysis(GFA)という新規解析手法を開発した(Nucleic Acid Res, 41, e62)。

Research Progress Status

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (51 results)

All 2013 2012 2011

All Journal Article (15 results) (of which Peer Reviewed: 10 results) Presentation (33 results) (of which Invited: 5 results) Book (3 results)

  • [Journal Article] p53 actions on microRNA expression and maturation pathway2013

    • Author(s)
      Suzuki HI
    • Journal Title

      Methods Mol Biol

      Volume: 962 Pages: 165-181

    • DOI

      10.1007/978-1-62703-236-0_14

    • ISBN
      9781627032353, 9781627032360
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Widespread inference of weighted microRNA-mediated gene regulation in cancer transcriptome analysis2013

    • Author(s)
      Suzuki HI
    • Journal Title

      Nucleic Acids Res

      Volume: 41 Issue: 5 Pages: e62-e62

    • DOI

      10.1093/nar/gks1439

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostate cancer cells and bone stromal cells mutually interact with each other through bone morphogenetic protein-mediated signals2012

    • Author(s)
      Nishimori H
    • Journal Title

      J Biol Chem

      Volume: 287 Issue: 24 Pages: 20037-20046

    • DOI

      10.1074/jbc.m112.353094

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sjogren syndrome antigen B (SSB)/La promotes global microRNA expression by binding microRNA precursors through stem-loop recognition.2012

    • Author(s)
      C Liang, et al.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 288(1) Issue: 1 Pages: 723-736

    • DOI

      10.1074/jbc.m112.401323

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Control of MicroRNA Maturation by p53 Tumor Suppressor and MCPIP1 Ribonuclease.2012

    • Author(s)
      HI Suzuki, et al.
    • Journal Title

      The Enzymes

      Volume: 32 Pages: 163-183

    • DOI

      10.1016/b978-0-12-404741-9.00008-8

    • ISBN
      9780124047419
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of human lung cancer-associated fibroblasts in three dimensional in vitro co-culture model2012

    • Author(s)
      Masafumi Horie, Akira Saito, Mitsuhiro Ohshima, Yasuyuki Morishita, Jun Nakajima, Tadashi Kohyama, Takahide Nagase
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 423 Issue: 2 Pages: 158-163

    • DOI

      10.1371/journal.pone.0056587

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] がんにおけるmiRNA生合成機構の異常と治療標的としての可能性2012

    • Author(s)
      鈴木洋,宮園浩平
    • Journal Title

      遺伝子医学MOOK

      Volume: 23 Pages: 214-218

    • Related Report
      2012 Annual Research Report
  • [Journal Article] microRNAプロセシングとがん制御シグナル経路のクロストーク2012

    • Author(s)
      鈴木洋,宮園浩平
    • Journal Title

      細胞

      Volume: 44(10) Pages: 448-451

    • Related Report
      2012 Annual Research Report
  • [Journal Article] がん抑制遺伝子p53によるマイクロRNAプロセシング制御の解明2012

    • Author(s)
      鈴木洋
    • Journal Title

      最新医学

      Volume: 67(9) Pages: 2050-2055

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 疾患モジュレーターとしての低分子RNA生合成機構2012

    • Author(s)
      鈴木洋,宮園浩平
    • Journal Title

      細胞

      Volume: 44(14) Pages: 589-592

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 慢性リンパ性白血病におけるmicroRNAの機能異常2012

    • Author(s)
      鈴木洋,宮園浩平
    • Journal Title

      血液内科

      Volume: 65(6) Pages: 846-852

    • NAID

      40019555265

    • Related Report
      2012 Annual Research Report
  • [Journal Article] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A2012

    • Author(s)
      Mihira H
    • Journal Title

      Journal of Biochemistry

      Volume: 151 Issue: 2 Pages: 145-156

    • DOI

      10.1093/jb/mvr121

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4α in HepG2 cells2011

    • Author(s)
      Kanki Y, Kohro T, Jiang S, Tsutsumi S, Mimura I, Suehiro JI,Wada Y, Ohta Y, Ihara S, Iwanari H, Naito M, Hamakubo T,Aburatani H, Kodama T, Minami T
    • Journal Title

      EMBO J

      Volume: 286 Issue: 34 Pages: 29848

    • DOI

      10.1074/jbc.m110.217745

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ALCLにおいてmiR-153bはNPM-ALKによる腫瘍形成、IL-17産生作用を仲介する2011

    • Author(s)
      松山浩徳
    • Journal Title

      Blood

      Volume: 118 Issue: 26 Pages: 6818-6892

    • DOI

      10.1182/blood-2011-05-354654

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MCPIP1はDicerに拮抗してmicroRNAのプロセシングを阻害する2011

    • Author(s)
      鈴木洋
    • Journal Title

      Mol Cell

      Volume: 44 Issue: 3 Pages: 424-436

    • DOI

      10.1016/j.molcel.2011.09.012

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Widespread inference of weighted microRNA-mediated gene regulation in cancer transcriptome analysis2013

    • Author(s)
      HI Suzuki, et al.
    • Organizer
      Keystone symposia “RNA Silencing”
    • Place of Presentation
      Whistler Conference Centre(カナダ)
    • Year and Date
      2013-03-22
    • Related Report
      2012 Annual Research Report
  • [Presentation] BMP-9/ALK-1 signals inhibit proliferation of lymphatic endothelial cells and reprogram them to blood vascular endothelial cells through down-regulation of Prox12013

    • Author(s)
      Y Yoshimatsu, et al.
    • Organizer
      9th Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association
    • Place of Presentation
      ハイアットリージェンシー(アメリカ合衆国)
    • Year and Date
      2013-02-24
    • Related Report
      2012 Annual Research Report
  • [Presentation] Widespread inference of weighted microRNA-mediated gene regulation in cancer transcriptome analysis2013

    • Author(s)
      HI Suzuki, et al.
    • Organizer
      9th Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association
    • Place of Presentation
      ハイアットリージェンシー(アメリカ合衆国)
    • Year and Date
      2013-02-23
    • Related Report
      2012 Annual Research Report
  • [Presentation] 低分子RNAの生合成機構の多様性と病態形成での役割に関する研究2013

    • Author(s)
      HI Suzuki.
    • Organizer
      新学術領域「RNA制御学」班会議
    • Place of Presentation
      レオパレス仙台(宮城県 仙台市)
    • Year and Date
      2013-01-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] BMP-9 inhibits proliferation of lymphatic endothelial cells and reprograms them to blood vascular endothelial cells through downregulation of Prox1 expression2012

    • Author(s)
      Y Yoshimatsu, et al.
    • Organizer
      第20回日本血管生物医学会学術集会
    • Place of Presentation
      あわぎんホール(徳島県 徳島市)
    • Year and Date
      2012-12-06
    • Related Report
      2012 Annual Research Report
  • [Presentation] Widespread inference of weighted microRNA-mediated gene regulation in cancer transcriptome analysis2012

    • Author(s)
      HI Suzuki, et al.
    • Organizer
      The 2nd International Symposium by JSPS Core-to-Core Program "Cooperative International Framework in TGF-β Family Signaling"
    • Place of Presentation
      昭和薬科大学(東京都 町田市)
    • Year and Date
      2012-10-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] BMP-9 inhibits proliferation of lymphatic endothelial cells and reprograms them to blood vascular endothelial cells through downregulation of Prox1 expression2012

    • Author(s)
      Y Yoshimatsu, et al.
    • Organizer
      The 2nd International Symposium by JSPS Core-to-Core Program "Cooperative International Framework in TGF-β Family Signaling"
    • Place of Presentation
      昭和薬科大学(東京都 町田市)
    • Year and Date
      2012-10-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] Complexity of microRNA biogenesis and Inference of small RNA network through transcriptome analysis2012

    • Author(s)
      HI Suzuki, K Miyazono.
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市教育文化会館(北海道 札幌市)
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] small RNA研究の最前線 ~microRNAの生合成と機能解析~2012

    • Author(s)
      HI Suzuki.
    • Organizer
      第5回 Symphony
    • Place of Presentation
      ホテルメトロポリタンエドモント飯田橋(東京都 千代田区)
    • Year and Date
      2012-09-02
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Specialization of microRNA biogenesis pathways and their alteration in human cancer2012

    • Author(s)
      HI Suzuki.
    • Organizer
      第22回広島がんセミナー・第4回JARIジョイント国際シンポジウム
    • Place of Presentation
      グランドプリンスホテル広島(広島県 広島市)
    • Year and Date
      2012-08-30
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] TGF-βによる内皮間葉移行におけるRhoシグナルとMRTF転写因子の役割2012

    • Author(s)
      H Mihira, HI Suzuki, et al.
    • Organizer
      第48回日本小児循環器学会
    • Place of Presentation
      国立京都国際会館(京都府 京都市)
    • Year and Date
      2012-07-05
    • Related Report
      2012 Annual Research Report
  • [Presentation] Negative regulation of miRNA biogenesis by MCPIP1 ribonuclease2012

    • Author(s)
      HI Suzuki.
    • Organizer
      RNAi, MicroRNAs, Single Cell Biology Stem Cells #8211; 2012 Meeting
    • Place of Presentation
      Hilton Garden Inn(アメリカ合衆国)
    • Year and Date
      2012-05-01
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 拡大する小さなRNAの世界 ~miRNAの生合成と癌における役割~2012

    • Author(s)
      HI Suzuki, K Miyazono.
    • Organizer
      日本分子生物学会 第12回 春季シンポジウム
    • Place of Presentation
      石和温泉慶山(山梨県 笛吹市)
    • Year and Date
      2012-04-25
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] MS-1血管内皮細胞におけるTGF-betaによる間葉細胞移行の分子機序2012

    • Author(s)
      H Mihira, HI Suzuki, et al.
    • Organizer
      第115回日本小児科学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡県 福岡市)
    • Year and Date
      2012-04-22
    • Related Report
      2012 Annual Research Report
  • [Presentation] マイクロRNAネットワークの分子基盤と病態制御2012

    • Author(s)
      HI Suzuki, K Miyazono
    • Organizer
      東京大学腎臓・内分泌内科リサーチカンファレンス
    • Place of Presentation
      東京大学医学部附属病院(東京都文京区)(招待講演)
    • Year and Date
      2012-02-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Termination of microRNA biogenesis by MCPIP1 ribonuclease through precursor miRNA degradation2012

    • Author(s)
      HI Suzuki, et al
    • Organizer
      Keystone symposia "Gene Silencing by Small RNAs"
    • Place of Presentation
      Fairmont Hotel Vancouver(カナダ)
    • Year and Date
      2012-02-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] microRNAシステムの異常と腫瘍病態のクロストーク2012

    • Author(s)
      HI Suzuki, K Miyazono
    • Organizer
      平成23年度文部科学省・厚生労働省合同公開シンポジウム
    • Place of Presentation
      学術総合センター(東京都千代田区)(招待講演)
    • Year and Date
      2012-01-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 低分子RNAの生合成機構の多様性と病態形成での役割に関する研究2012

    • Author(s)
      HI Suzuki
    • Organizer
      新学術領域「RNA制御学」班会議
    • Place of Presentation
      ニチイ学館神戸ポートアイランドセンター(兵庫県神戸市)
    • Year and Date
      2012-01-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] microRNA regulation of tumor immunophenotype and microenvironment2012

    • Author(s)
      HI Suzuki, et al
    • Organizer
      日本学術振興会先端研究拠点事業「TGF-βファミリーシグナル国際共同研究拠点」第1回国際シンポジウム
    • Place of Presentation
      東京大学小柴ホール(東京都文京区)
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGF-β2 induces endothelial-mesenchymal transition of MS-1 endothelial cells2012

    • Author(s)
      H Mihira, HI Suzuki, et al
    • Organizer
      日本学術振興会先端研究拠点事業「TGF-βファミリーシグナル国際共同研究拠点」第1回国際シンポジウム
    • Place of Presentation
      東京大学小柴ホール(東京都文京区)
    • Related Report
      2011 Annual Research Report
  • [Presentation] MCPIP1 ribonuclease antagonizes Dicer and terminates microRNA biogenesis through precursor microRNA degradation2012

    • Author(s)
      HI Suzuki, et al
    • Organizer
      東京大学グローバルCOE"生体シグナルを基盤とする統合生命学"第5回グローバルCOEリトリート
    • Place of Presentation
      八ヶ岳ロイヤルホテル(山梨県北杜市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGF-β2 induces endothelial-mesenchymal transition of MS-1 endothelial cells2012

    • Author(s)
      H Mihira, HI Suzuki, et al
    • Organizer
      東京大学グローバルCOE"生体シグナルを基盤とする統合生命学"第5回グローバルCOEリトリート
    • Place of Presentation
      八ヶ岳ロイヤルホテル(山梨県北杜市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Negative regulation of miRNA biogenesis by MCPIP1 ribonuclease2011

    • Author(s)
      HI Suzuki, K Miyazono
    • Organizer
      Tokyo RNA Club The 8th meeting
    • Place of Presentation
      慶応義塾大学(東京都新宿区)(招待講演)
    • Year and Date
      2011-12-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGF-β2 induces endothelial-nesenchymal transition of MS-1 endothelial cells2011

    • Author(s)
      H Mihira, HI Suzuki, et al
    • Organizer
      第11回東京大学生命科学シンポジウム
    • Place of Presentation
      東京大学工学部(東京都文京区)
    • Year and Date
      2011-11-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] Regulation of microRNA biogenesis and cancer2011

    • Author(s)
      HI Suzuki, K Miyazono
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)(招待講演)
    • Year and Date
      2011-10-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] A novel abortive processing machinery in microRNA biogenesis2011

    • Author(s)
      HI Suzuki, K Miyazono
    • Organizer
      第84回日本生化学会
    • Place of Presentation
      国立京都国際会館(京都府京都市)(招待講演)
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] A novel regulatory system in microRNA biogenesis2011

    • Author(s)
      HI Suzuki, K Miyazono
    • Organizer
      第3回日本RNAi研究会
    • Place of Presentation
      グランドプリンスホテル広島(広島県広島市)(招待講演)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] microRNAs in oncogenic networks2011

    • Author(s)
      HI Suzuki, K Miyazono
    • Organizer
      第15回日本がん分子標的治療学会
    • Place of Presentation
      ホテル日航東京(東京都港区)(招待講演)
    • Year and Date
      2011-06-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGF-β2 induces endothelial-mesenchymal transition of MS-1 endothelial cells2011

    • Author(s)
      H Mihira, HI Suzuki, et al
    • Organizer
      7th Congress of Asian Society for Pediatric Research
    • Place of Presentation
      Colorado Convention Center(アメリカ合衆国)
    • Year and Date
      2011-05-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Regulation of microRNA expression and maturation pathway by p532011

    • Author(s)
      HI Suzuki, K Miyazono
    • Organizer
      第100回病理学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)(招待講演)
    • Year and Date
      2011-04-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A2011

    • Author(s)
      H Mihira, HI Suzuki, et al
    • Organizer
      第114回日本小児科学会学術集会
    • Place of Presentation
      グランドプリンスホテル新高輪国際館パミール(東京都港区)
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A2011

    • Author(s)
      T Watabe, et al
    • Organizer
      TGF-β Meeting
    • Place of Presentation
      Ludwig Cancer Institute(スウェーデン)
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A2011

    • Author(s)
      H Mihira, HI Suzuki, et al
    • Organizer
      第19回日本血管生物医学会
    • Place of Presentation
      東京ステーションコンファレンス(東京都千代田区)
    • Related Report
      2011 Annual Research Report
  • [Book] がん増殖と悪性化の分子機構(宮澤恵二・伊藤進 編) 9章 がんとmicroRNA2012

    • Author(s)
      鈴木洋
    • Publisher
      化学同人
    • Related Report
      2012 Annual Research Report
  • [Book] がん増殖と悪性化の分子機構(宮澤恵二・伊藤進 編) 11章 がんとオートファジー2012

    • Author(s)
      鈴木洋
    • Publisher
      化学同人
    • Related Report
      2012 Annual Research Report
  • [Book] デヴィータがんの分子生物学 30章 リンパ腫2012

    • Author(s)
      鈴木洋
    • Publisher
      メディカル・サイエンス・インターナショナル
    • Related Report
      2012 Annual Research Report

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Published: 2011-04-06   Modified: 2018-03-28  

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