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Analysis of epigenetic regulation of androgen responsive miRNAs in prostate cancer

Research Project

Project/Area Number 16K18411
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionNippon Medical School

Principal Investigator

Misawa Aya  日本医科大学, 医学部, 講師 (20598453)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
KeywordslncRNA / 転移 / エピジェネティクス / ncRNA / 骨転移 / 前立腺癌 / 石灰化 / ALPL / HOTAIR / 前立腺がん / TNSAP / miRNA / AR / TNAP
Outline of Final Research Achievements

HOTAIR is a lncRNA that plays critical role in gene regulation and chromatin dynamics through epigenetic mechanisms. In this work we studied the physiological role of HOTAIR during the process of mineralization using osteoblastic osteosarcoma cells focusing in ALPL Tissue Non-Specific Alkaline Phosphatase), a pivotal gene that controls bone formation. HOTAIR knockdown resulted in upregulation of ALPL, increase of alkaline phosphatase (ALP) activity and enhance d mineralization in osteoblastic SaOS-2 cells cultured in mineralizing medium. Luciferase assays using reporter vector s containing ALPL promoter showed that HOTAIR repression increases ALPL promoter activity. Furthermore, HOTAIR knockdown increased histone H3K4 methylation levels at ALPL promoter region, suggesting that ALPL repression by HOTAIR is regulated by epigenetic mechanisms. This work supports that physiological bone formation is epigenetically regulated by a lncRNA.

Academic Significance and Societal Importance of the Research Achievements

骨の石灰化において中心的な役割を果たすALPL は転移性前立腺がんの増殖に関与していることが報告されている。従って、HOTAIR が ALPL を制御することによって骨の石灰化のみならず、前立腺がんの骨転移にも関与している可能性がある。実際、骨転移した前立腺がんより樹立された VCaP 細胞株は ALPL を発現しており、石灰化することを確認した。前立腺がん細胞は転移巣である骨に到達すると骨特有の性質を示すことが示唆され、本研究は前立腺癌及び骨に転移する他の癌の骨転移のメカニズムに関して新たな手掛かりを与える研究となった。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (5 results)

  • [Journal Article] Androgen-induced lncRNA POTEF-AS1 regulates apoptosis-related pathway to facilitate cell survival in prostate cancer cells.2017

    • Author(s)
      Misawa A, Takayama KI, Fujimura T, Homma Y, Suzuki Y, Inoue S
    • Journal Title

      Cancer Sci

      Volume: 108(3) Issue: 3 Pages: 373-379

    • DOI

      10.1111/cas.13151

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / 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] 癌の骨転移に関与する lncRNA の分子解剖学的解析2019

    • Author(s)
      三沢彩、近藤幸尋、武井寛幸、瀧澤俊広
    • Organizer
      124回日本解剖学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 前立腺癌の骨転移に関与する lncRNA の同定及び機能解析2018

    • Author(s)
      三沢彩、瀧澤俊広
    • Organizer
      第77回日本癌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト骨肉腫細胞における lncRNA による ALPL のエピジェネティック制御機構の解析2018

    • Author(s)
      三沢 彩
    • Organizer
      第12回 ALPS 研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒト骨肉腫細胞における HOTAIR による ALPL のエピジェネティックな制御機構の解析2018

    • Author(s)
      三沢 彩
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒト骨芽細胞様骨肉腫細胞における HOTAIR による ALPL のエピジェネティックな制御機構の解析2018

    • Author(s)
      三沢 彩
    • Organizer
      第123回日本解剖学会総会全国学術集会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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