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Functional analysis of prostate cancer bone metastasis-related lncRNA and establishment of the basis for the development of new therapies

Research Project

Project/Area Number 18K09181
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionInternational University of Health and Welfare (2021-2022)
Keio University (2020)
Nippon Medical School (2018-2019)

Principal Investigator

Misawa Aya  国際医療福祉大学, 医学部, 講師 (20598453)

Co-Investigator(Kenkyū-buntansha) 瀧澤 俊広  日本医科大学, 大学院医学研究科, 大学院教授 (90271220)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordslncRNA / 前立腺がん / 骨転移 / サイトカイン / インテグリン / 代謝 / T 細胞 / 免疫チェックポイント阻害薬 / エネルギー代謝 / ncRNA / 前立腺癌 / 細胞外小胞体 / 癌微小環境 / Osteomimicry
Outline of Final Research Achievements

In this study, we found that homeobox A11 antisense RNA (HOXA11-AS), a highly expressed lncRNA in cell lines derived from prostate cancer bone metastases, promotes cell invasion and proliferation of PC3 prostate cancer cells. Transcription factor homeobox B13 (HOXB13) was identified as an upstream regulator of HOXA11-AS. HOXA11-AS regulated bone metastasis-associated C-C motif chemokine ligand 2 (CCL2)/C-C chemokine receptor type 2 (CCR2) signaling in both PC3 prostate cancer cells and SaOS2 osteoblastic cells. The HOXB13/HOXA11-AS axis also regulated integrin subunits specific to prostate cancer bone metastasis. Furthermore, conditioned medium containing HOXA11-AS secreted from PC3 cells could induce the expression of CCL2 and IBSP in SaOS2 osteoblastic cells. These results suggest that prostate cancer HOXA11-AS and HOXB13 promote metastasis by regulation of CCL2/CCR2 and integrin signals in autocrine and paracrine manners.

Academic Significance and Societal Importance of the Research Achievements

lncRNA は多様な臓器のがんで異常発現することが知られている。HOXA11-AS はがんバイオマーカーとして同定されている免疫関連 lncRNAである。本研究より、HOXA11-ASが前立腺がんの骨転移に主要な役割を果たしていることが示唆された。また、lncRNA が免疫チェックポイント阻害剤との奏効と相関する結果も得られており、HOXA11-ASと発がんとの関係の解明は抗がん剤治療や免疫療法を組み合わせた新たな複合療法の開発につながることが期待できる。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2022 2021 2019 2018

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

  • [Journal Article] Melanoma antigens recognized by T cells and their use for immunotherapy2022

    • Author(s)
      Shigeki Ohta, Aya Misawa, Chaw Kyi-Tha-Thu, Naomi Matsumoto, Yoshie Hirose, Yutaka Kawakami
    • Journal Title

      Exp Dermatol

      Volume: 32(3) Issue: 3 Pages: 297-305

    • DOI

      10.1111/exd.14741

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long Noncoding RNA HOXA11-AS and Transcription Factor HOXB13 Modulate the Expression of Bone Metastasis-Related Genes in Prostate Cancer2021

    • Author(s)
      Aya Misawa, Yukihiro Kondo, Hiroyuki Takei and Toshihiro Takizawa
    • Journal Title

      Genes

      Volume: 12(182) Issue: 2 Pages: 1-19

    • DOI

      10.3390/genes12020182

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] CASC may be involved in anti-tumor immune response through the modulation of NAD+ dependent energy metabolism2022

    • Author(s)
      Aya Misawa
    • Organizer
      第81回日本癌学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 分子解剖学的アプローチによる癌の骨転移における HOXA11-AS の機能解明2019

    • Author(s)
      三沢彩、近藤幸尋、武井寛幸、瀧澤俊広
    • Organizer
      第125回日本解剖学会総会全国学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 癌の骨転移に関与する lncRNA の機能解析2019

    • Author(s)
      三沢彩、近藤幸尋、武井寛幸、瀧澤俊広
    • Organizer
      第78回日本癌学会
    • Related Report
      2019 Research-status Report
  • [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
      第124回日本解剖学会総会全国学術集会
    • Related Report
      2018 Research-status 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 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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