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microRNA-125b inhibits tumor vascular formation through translational suppression of VE-cadherin

Research Project

Project/Area Number 23701054
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionOsaka University

Principal Investigator

KIDOYA Hiroyasu  大阪大学, 微生物病研究所, 助教 (00543886)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsマイクロRNA / 血管新生 / 細胞接着 / 癌治療 / 核酸医薬 / 腫瘍血管新生 / 癌研究 / miRNA
Research Abstract

MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that function as negative regulators of gene expression. Posttranscriptional regulation by miRNAs is important for many aspects of development and disease. Sveral miRNAs are highly expressed in endothelial cells. Whereas the specific functions of miRNAs for tumor angiogenesis are less clear.
Here, we identified miRNAs that were enriched in endothelial cells derived from LLC tumor. We found that miR-125b regulated the expression of endothelial cell adherent protein VE-cadherin. Additionally, overexpression of miR-125b in endothelial cells resulted in inhibition of proliferation, tube formation and migration activity. Furthermore, in vivo transfection of mir-125b in subcutaneous implanted LLC tumor, inhibited neo vascular formation and suppressed tumor growth.
These findings illustrate that mir-125b act as negative regulator of tumor angiogenesis and providing a new target for modulating vascular formation and function.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (48 results)

All 2014 2013 2012 2011 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (20 results) (of which Invited: 2 results) Book (2 results) Remarks (8 results)

  • [Journal Article] Apelin inhibits diet-induced obesity by enhancing lymphatic and blood vessel integrity.2013

    • Author(s)
      Sawane M, Kajiya K, Kidoya H, Takagi M, Muramatsu F, Takakura N.
    • Journal Title

      Diabetes.

      Volume: 62(6) Issue: 6 Pages: 1970-1980

    • DOI

      10.2337/db12-0604

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of Trib1 for the differentiation of adipose tissue-resident macrophages maintaining metabolic homeostasis.2013

    • Author(s)
      Satoh T, Kidoya H, Naito H, Yamamoto M, Takemura N, Nakagawa K, Yoshioka Y, Morii E, Takakura N, Takeuchi O, Akira S
    • Journal Title

      Nature

      Volume: 495(7442) Issue: 7442 Pages: 524-528

    • DOI

      10.1038/nature11930

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumor endothelial cell-specific drug delivery system using apelin-conjugated liposomes.2013

    • Author(s)
      Kawahara H, Naito H, Takara K, Wakabayashi T, Kidoya H, Takakura N.
    • Journal Title

      PLos One

      Volume: 8 Issue: 6 Pages: e65499-e65499

    • DOI

      10.1371/journal.pone.0065499

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Galectin-3 accelerates m2 macrophage infiltration and angiogenesis in tumors.2013

    • Author(s)
      Jia W
    • Journal Title

      Am J Pathol.

      Volume: 182 Issue: 5 Pages: 1821-1831

    • DOI

      10.1016/j.ajpath.2013.01.017

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ligand-independent Tie2 dimers mediate kinase activity stimulated by high dose angiopoietin-1.2013

    • Author(s)
      Yamakawa D
    • Journal Title

      J Biol Chem.

      Volume: 288 Issue: 18 Pages: 12469-12477

    • DOI

      10.1074/jbc.m112.433979

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of vascular endothelial side population cells in the choroidal vessels and their potential role in age-related macular degeneration.2013

    • Author(s)
      Wakabayashi T, Naito H, Takara K, Kidoya H, Sakimoto S, Oshima Y, Nishida K, Takakura N
    • Journal Title

      Investigative Ophthalmology & Visual Science

      Volume: 54 Issue: 10 Pages: 6686-6693

    • DOI

      10.1167/iovs.13-12342

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An angiogenic role for adrenomedullin in choroidal neovascularization.2013

    • Author(s)
      Sakimoto S, Kidoya H, Kamei M, Naito H, Yamakawa D, Sakaguchi H, Wakabayashi T, Nishida K, Takakura N.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 3 Pages: e58096-e58096

    • DOI

      10.1371/journal.pone.0058096

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The apelin/APJ system induces maturation of the tumor vasculature and improves the efficiency of immune therapy2012

    • Author(s)
      Kidoya H.
    • Journal Title

      Oncogene

      Volume: (In press) Issue: 27 Pages: 3254-64

    • DOI

      10.1038/onc.2011.489

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice2012

    • Author(s)
      Sakimoto S.
    • Journal Title

      Development

      Volume: (In press) Issue: 7 Pages: 1327-1335

    • DOI

      10.1242/dev.072330

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] microRNA-125b inhibits tube formation of blood vessels through translational suppression of VE-cadherin2012

    • Author(s)
      Muramatsu F.
    • Journal Title

      Oncogene

      Volume: (In press) Issue: 4 Pages: 414-421

    • DOI

      10.1038/onc.2012.68

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biology of the apelin-APJ axis in vascular formation.2012

    • Author(s)
      Kidoya H, Takakura N.
    • Journal Title

      J Biochem

      Volume: 152(2) Issue: 2 Pages: 125-131

    • DOI

      10.1093/jb/mvs071

    • NAID

      10031166121

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The apelin/APJ system induces maturation of the tumor vasculature and improves the efficiency of immune therapy.2012

    • Author(s)
      Kidoya H, Kunii N, Naito H, Muramatsu F, Okamoto Y, Nakayama T, Takakura N.
    • Journal Title

      Oncogene

      Volume: 31(27) Pages: 3254-3264

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Promotion of Lymphatic Integrity by Angiopoietin-1/Tie2 Signaling during Inflammation2012

    • Author(s)
      Kajiya K.
    • Journal Title

      Am J Pathol.

      Volume: 180 Issue: 3 Pages: 1273-1282

    • DOI

      10.1016/j.ajpath.2011.11.008

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] The transcription factor Jun dimerization protein 2 controls bone homeostasis and antibacterial immunity by regulating osteoclast and neutrophil differentiation2012

    • Author(s)
      kenta Maruyama, Masahiro Fukasaka, Alexis Vandenbon, Tatsuya Saitoh, Takumi Kawasaki, Takeshi Kondo, Kazunari K. Yokoyama, Hiroyasu Kidoya, Nobuyuki Takakura, Daron Standley, Osamu Takeuchi, and Shizuo Akira
    • Journal Title

      Immunity

      Volume: 37 Issue: 6 Pages: 1024-1036

    • DOI

      10.1016/j.immuni.2012.08.022

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of a resident vascular stem/ progenitor cell population in preexisting blood vessels2011

    • Author(s)
      Naito H, Kidoya H, Sakimoto S, Wakabayashi T, Takakura N
    • Journal Title

      EMBO J.

      Volume: 31 Issue: 4 Pages: 842-855

    • DOI

      10.1038/emboj.2011.465

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Apelin attenuates UVB-induced edema and inflammation by promoting vessel function2011

    • Author(s)
      Sawane M.
    • Journal Title

      Am J Pathol.

      Volume: 179 Issue: 6 Pages: 2691-2697

    • DOI

      10.1016/j.ajpath.2011.08.024

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 2-Methoxycinnamaldehyde inhibits tumor angiogenesis by suppressing Tie2 activation2011

    • Author(s)
      Yamakawa D.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 415 Issue: 1 Pages: 174-180

    • DOI

      10.1016/j.bbrc.2011.10.053

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Changes in blood vessel maturation in the fibrous cap of the tumor rim2011

    • Author(s)
      Naito H.
    • Journal Title

      Cancer Sci.

      Volume: 103 Issue: 3 Pages: 433-438

    • DOI

      10.1111/j.1349-7006.2011.02157.x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Keystone Symposia meeting on : Metabolism and Angiogenesis2014

    • Author(s)
      Hiroyasu Kidoya
    • Organizer
      Role of apelin-APJ system in regulation of tumor vascular normalization
    • Place of Presentation
      Whistler Conference Centre, Whistler, British Columbia, Canada
    • Related Report
      2013 Final Research Report
  • [Presentation] microRNA-125b inhibits tumor vascular formation through translational suppression of VE-cadherin2014

    • Author(s)
      Hiroyasu Kidoya
    • Organizer
      がん支援冬期シンポジウム
    • Place of Presentation
      東京都・千代田区
    • Related Report
      2013 Final Research Report
  • [Presentation] microRNA-125b inhibits tumor vascular formation through translational suppression of VE-cadherin.2014

    • Author(s)
      Hiroyasu Kidoya.
    • Organizer
      がん支援冬期シンポジウム
    • Place of Presentation
      東京都・千代田区
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of apelin-APJ system in regulation of tumor vascular normalization.2014

    • Author(s)
      H Kidoya; H Naito; C Takeshita; F Muramatsu; N Takakura.
    • Organizer
      Keystone Symposia meeting on: Metabolism and Angiogenesis.
    • Place of Presentation
      カナダ・ウイスラー
    • Related Report
      2013 Annual Research Report
  • [Presentation] 血管の「質」と「構造」を制御する分子機構 -Molecular mechanisms of blood vessel maturation andremodeling2013

    • Author(s)
      Hiroyasu Kidoya
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      兵庫県・神戸市
    • Related Report
      2013 Final Research Report
  • [Presentation] Tumor vessel maturation by apelin/APJ system improves the efficiency of immunotherapy2013

    • Author(s)
      Hiroyasu Kidoya
    • Organizer
      The European Cancer Congress 2013
    • Place of Presentation
      オランダ・アムステルダム
    • Related Report
      2013 Final Research Report
  • [Presentation] Tumor vessel maturation by apelin/APJ system improves the efficiency of immunotherapy.2013

    • Author(s)
      H. Kidoya, N. Kunii, H. Naito, C. Takeshita, N. Takakura.
    • Organizer
      The European Cancer Congress 2013
    • Place of Presentation
      オランダ・アムステルダム
    • Related Report
      2013 Annual Research Report
  • [Presentation] 血管の「質」と「構造」を制御する分子機構 -Molecular mechanisms of blood vessel maturation and remodeling.2013

    • Author(s)
      Hiroyasu Kidoya, Hisamichi Naito, Naoki Kunii, Nobuyuki Takakura.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      兵庫県・神戸市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Regulation of vascular maturation by apelin-APJ and itsapplication for angiogenic therapy2012

    • Author(s)
      Hiroyasu Kidoya
    • Organizer
      第20回日本血管生物医学会学術集会 The 10th Korea-Japan Joint Symposium on VascularBiology
    • Place of Presentation
      徳島
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of secreted frizzled-related protein-1 in tumorangiogenesis、ポスター2012

    • Author(s)
      Hiroyasu Kidoya
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Maturation Of The Tumor Blood Vessels Induced By Apelin/APJ System Improves The Efficiency Of Immunotherapy2012

    • Author(s)
      Hiroyasu Kidoya
    • Organizer
      Cell symposia : Angiogenesis, Metabolic Regulation, and Cancer Biology in association with VIB
    • Place of Presentation
      Katholieke Universiteit, Leuven, Belgium
    • Related Report
      2013 Final Research Report
  • [Presentation] 血管成熟化因子「Apelin」を用いた、新概念の血管再生療法の開発2012

    • Author(s)
      木戸屋浩康
    • Organizer
      第49回日本臨床分子医学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 血管成熟化因子「Apelin」を用いた、新概念の血管再生療法の開発2012

    • Author(s)
      木戸屋浩康、高倉伸幸
    • Organizer
      第49回日本臨床分子医学会学術集会
    • Place of Presentation
      京都、2012年4月13日-14
    • Related Report
      2012 Research-status Report
  • [Presentation] Maturation Of The Tumor Blood Vessels Induced By Apelin/APJ System Improves The Efficiency Of Immunotherapy.2012

    • Author(s)
      H. Kidoya, N. Kunii, H. Naito, F. Muramatsu, N. Takakura.
    • Organizer
      Cell symposia: Angiogenesis, Metabolic Regulation, and Cancer Biology in association with VIB
    • Place of Presentation
      Katholieke Universiteit, Leuven, Belgium.
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of secreted frizzled-related protein-1 in tumor angiogenesis.2012

    • Author(s)
      Hiroyasu Kidoya, Nobuyuki Takakura.
    • Organizer
      第71回 日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Regulation of vascular maturation by apelin-APJ and its application for angiogenic therapy.2012

    • Author(s)
      Hiroyasu Kidoya, Nobuyuki TakakuraHiroyasu Kidoya, Hisamichi Naito, Naoki Kunii, Nobuyuki Takakura.
    • Organizer
      第20回日本血管生物医学会学術集会 The 10th Korea-Japan Joint Symposium on Vascular Biology
    • Place of Presentation
      徳島
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Maturation of the tumor blood vessels induced by apelin/APJ system improves the efficiency of immunotherapy2011

    • Author(s)
      Hiroyasu Kidoya
    • Organizer
      The Second Pacific Symposium on Vascular Biology
    • Place of Presentation
      Jeju Island, Korea
    • Related Report
      2013 Final Research Report
  • [Presentation] microRNA-125b inhibits tumor vascular formation through translational suppression of VE-cadherin2011

    • Author(s)
      Hiroyasu Kidoya
    • Organizer
      The 9th Japan-Korea Joint Symposium on Vascular Biology
    • Place of Presentation
      Busan, Korea
    • Related Report
      2013 Final Research Report
  • [Presentation] microRNA-125b inhibits tumor vascular formation2011

    • Author(s)
      Hiroyasu Kidoya, et al.
    • Organizer
      9th Japan-Korea Joint Symposium on VascularBiology
    • Place of Presentation
      Busan, Korea
    • Related Report
      2011 Research-status Report
  • [Presentation] Maturation of the tumor blood vessels induced2011

    • Author(s)
      Hiroyasu Kidoya, et al.
    • Organizer
      The Second Pacific Symposium on Vascular Biology
    • Place of Presentation
      Jeju Island, Korea.
    • Related Report
      2011 Research-status Report
  • [Book] 血管医学2013

    • Author(s)
      村松史隆,木戸屋浩康,高倉伸幸
    • Total Pages
      14
    • Publisher
      メディカルレビュー社
    • Related Report
      2013 Final Research Report
  • [Book] 2013年12月号2013

    • Author(s)
      村松史隆/木戸屋浩康/高倉伸幸
    • Total Pages
      6
    • Publisher
      メディカルレビュー社
    • Related Report
      2013 Annual Research Report
  • [Remarks] 微生物病研究所ホームページ

    • URL

      http://st.biken.osaka-u.ac.jp/member/kidoya.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 大阪大学研究者総覧

    • URL

      http://www.dma.jim.osaka-u.ac.jp/view?l=ja&u=7708

    • Related Report
      2013 Final Research Report
  • [Remarks] 大阪大学 微生物病研究所 情報伝達分野 HP

    • URL

      http://st.biken.osaka-u.ac.jp/member/kidoya.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 大阪大学 研究者総覧

    • URL

      http://www.dma.jim.osaka-u.ac.jp/kg-portal/aspi/RX0011D.asp?UNO=19906&seq=1206

    • Related Report
      2013 Annual Research Report
  • [Remarks] 微生物病研究所ホームページ

    • URL

      http://st.biken.osaka-u.ac.jp/member/kidoya.html

    • Related Report
      2012 Research-status Report
  • [Remarks] 大阪大学 研究者総覧

    • URL

      http://www.dma.jim.osaka-u.ac.jp/view?l=ja&u=7708

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://st.biken.osaka-u.ac.jp/member/kidoya.html

    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://bsw3.naist.jp/takahashi/neurovascular/member2.html#kidoya

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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