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Functional analysis and clinical application of secreted long noncoding RNAs derived from extracellular vesicles that modulate cancer microenvironment

Research Project

Project/Area Number 16K15496
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Endocrinology
Research InstitutionSaitama Medical University

Principal Investigator

HORIE KUNIKO  埼玉医科大学, 医学部, 教授 (90261982)

Co-Investigator(Kenkyū-buntansha) 高山 賢一  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50508075)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsエクソソーム / 非コードRNA / がん微小環境 / ホルモン依存性がん / 内科
Outline of Final Research Achievements

The role of immune-related factor EBAG9 in cancer microenvironment was analyzed in terms of a secreted molecule mediated from cancer extracellular vesicles, or exosomes. Exosomes were isolated from EBAG9-overexpressing prostate cancer cells and transferred into another prostate cancer cells, leading to an increase in cell motility. Exosomes from EBAG9-overexpressing cancer cells further repressed the cytotoxicity of T lymphocytes against prostate cancer cells. The suppression of T-cell cytotoxicity was recovered by anti-EBAG9 neutralizing antibody. Overall, the study shows that EBAG9 mediated from cancer exosomes will contribute to cancer progression by modulating the microenvironment.
Small RNA sequencing for several endometrial cancer cells identified common microRNAs abundantly expressed in the cells. Among them, one microRNA was further analyzed as it promotes cancer cell proliferation, and its target gene was identified based on in silico and functional analyses.

Report

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

    (12 results)

All 2018 2017 2016 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (4 results) (of which Invited: 3 results) Remarks (1 results)

  • [Journal Article] Extracellular vesicle-mediated EBAG9 transfer from cancer cells to tumor microenvironment promotes immune escape and tumor progression2018

    • Author(s)
      Miyazaki Toshiaki、Ikeda Kazuhiro、Sato Wataru、Horie-Inoue Kuniko、Inoue Satoshi
    • Journal Title

      Oncogenesis

      Volume: 7 Issue: 1 Pages: 7-7

    • DOI

      10.1038/s41389-017-0022-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prostate cancer-associated lncRNAs2018

    • Author(s)
      Mitobe Yuichi、Takayama Ken-ichi、Horie-Inoue Kuniko、Inoue Satoshi
    • Journal Title

      Cancer Letters

      Volume: 418 Pages: 159-166

    • DOI

      10.1016/j.canlet.2018.01.012

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteasome 26S subunit PSMD1 regulates breast cancer cell growth through p53 protein degradation2018

    • Author(s)
      Okumura T,Ikeda K,Sato W,Horie-Inoue K,Takeda S,Inoue S
    • Journal Title

      J Biochem

      Volume: 163 Issue: 1 Pages: 19

    • DOI

      10.1093/jb/mvx053

    • NAID

      40021457346

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRIM44 Is a Poor Prognostic Factor for Breast Cancer Patients as a Modulator of NF-κB Signaling2017

    • Author(s)
      Kawabata Hidetaka、Azuma Kotaro、Ikeda Kazuhiro、Sugitani Ikuko、Kinowaki Keiichi、Fujii Takeshi、Osaki Akihiko、Saeki Toshiaki、Horie-Inoue Kuniko、Inoue Satoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 9 Pages: 1931-1931

    • DOI

      10.3390/ijms18091931

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ABHD2, an androgen target gene, promotes prostate cancer cell proliferation and migration.2016

    • Author(s)
      Obinata D, Takada S, Takayama K, Urano T, Ito A, Ashikari D, Fujiwara K, Yamada Y, Murata T, Kumagai J, Fujimura T, Ikeda K, Horie-Inoue K, Homma Y
    • Journal Title

      Eur J Cancer 57

      Volume: 57 Pages: 39-49

    • DOI

      10.1016/j.ejca.2016.01.002

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Estrogen modulates exercise endurance along with mitochondrial uncoupling protein 3 downregulation in skeletal muscle of female mice.2016

    • Author(s)
      Nagai S, Ikeda K, Horie-Inoue K, Shiba S, Nagasawa S, Takeda S, Inoue S.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 480 Issue: 4 Pages: 758-784

    • DOI

      10.1016/j.bbrc.2016.10.129

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Androgen-induced lncRNA SOCS2-AS1 promotes cell growth and inhibits apoptosis in prostate cancer cells.2016

    • Author(s)
      Misawa A, Takayama K, Urano T, Inoue S
    • Journal Title

      J Biol Chem

      Volume: 291(34) Issue: 34 Pages: 17861-17880

    • DOI

      10.1074/jbc.m116.718536

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] An Estrogen-Regulated Long Noncoding RNA That Modulates Breast Cancer Growth2018

    • Author(s)
      Kuniko Horie-Inoue, Kazuhiro Ikeda, Yuichi Mitobe, Satoshi Inoue
    • Organizer
      ENDO 2018(米国内分泌学会2018年会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 治療抵抗性乳がんの病態に関わる分子ネットワーク解明への取組み2017

    • Author(s)
      堀江 公仁子
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] エストロゲン受容体シグナルに関連し治療抵抗性乳がんの病態に関わる長鎖非コードRNA2017

    • Author(s)
      堀江 公仁子、水戸部 悠一、池田 和博、井上 聡
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Functional shRNA library screening and sequencing-based identification of coding and non-coding RNAs that associate with the biology of hormone refractory cancers.2016

    • Author(s)
      Kuniko Horie
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report
    • Invited
  • [Remarks] 埼玉医科大学ゲノム医学研究センター遺伝子情報制御部門

    • URL

      http://www.saitama-med.ac.jp/genome/Div02_GRST/index.html

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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