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Involvement of the epigenetic aberration of hypoxia inducible factor 2 (HIF2) in development of uterine leiomyoma

Research Project

Project/Area Number 26861329
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionYamaguchi University

Principal Investigator

MAEKAWA Ryo  山口大学, 医学部附属病院, 助教 (90598749)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
KeywordsDNAメチル化 / NRG1 / 子宮筋腫 / EGR / HIF2 / mRNA発現 / 低酸素
Outline of Final Research Achievements

To obtain master gene candidates that may have key roles in the development of uterine leiomyomas (ULs), we first performed network analysis by combining genome-wide mRNA expression data, protein-protein gene interaction network data and genome-wide DNA methylation data. Then we obtained 5 master gene candidates. Of 5 candidate genes, we focused on HIF2 and NRG1. In ULs, HIF2 expression is downregulated with DNA hypermethylation and NRG1 is upregulated with DNA hypermethylation. Force expression of NRG1 in uterine smooth muscle cells (UtSMCs) showed several signaling pathways such as TGF-beta signaling and Wnt/beta-catenin signaling, that has been shown to be upregulated in ULs. Knockdown of HIF2 was not succeeded because the UtSMCs did not show enough levels of HIF2 expression. The results suggest that NRG1 is involved in the pathogenesis and development in ULs.

Report

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

    (6 results)

All 2015 2014

All Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] 子宮筋腫におけるトランスクリプトームとエピゲノムを統合した蛋白質間相互ネットワーク解析2015

    • Author(s)
      前川 亮
    • Organizer
      第9回日本エピジェネティクス研究会年会
    • Place of Presentation
      東京都千代田区(学術総合センター一橋講堂)
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] Epigenome-transcriptome-interactome approach facilitates the investigation of underlying epigenetical deregulation in uterine leiomyomas2015

    • Author(s)
      Ryo Maekawa
    • Organizer
      IFFS international meeting 2015
    • Place of Presentation
      神奈川県横浜市(パシフィコ横浜)
    • Year and Date
      2015-04-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 子宮筋腫におけるトランスクリプトームとエピゲノムを統合した蛋白質間相互ネットワーク解析2015

    • Author(s)
      前川 亮
    • Organizer
      第88回日本内分泌学会学術集会
    • Place of Presentation
      東京都千代田区(ホテルニューオータニ)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 子宮筋腫におけるトランスクリプトームとエピゲノムを統合した蛋白質間相互ネットワーク解析2015

    • Author(s)
      前川 亮
    • Organizer
      第19回日本生殖内分泌学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪市)
    • Year and Date
      2015-01-10
    • Related Report
      2014 Research-status Report
  • [Presentation] 子宮筋腫におけるトランスクリプトームとエピゲノムを統合した蛋白質間相互ネットワーク解析2014

    • Author(s)
      前川 亮
    • Organizer
      日本産婦人科学会中国四国学術講演会
    • Place of Presentation
      ANAクラウンプラザホテル(宇部市)
    • Year and Date
      2014-09-11 – 2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Epigenome-interactome approach facilitates the investigation of underlying epigenetical deregulation in uterine leiomyomas2014

    • Author(s)
      RYO MAEKAWA
    • Organizer
      Society for the study of reproduction
    • Place of Presentation
      Grand Rapids, Michigan, USA
    • Year and Date
      2014-07-19 – 2014-07-23
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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