• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Involvement of lnc162 on sensitivity to DNA demethylating agents

Research Project

Project/Area Number 18H02704
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionNational Cancer Center Japan

Principal Investigator

Ushijima Toshikazu  国立研究開発法人国立がん研究センター, 研究所, 分野長 (90232818)

Co-Investigator(Kenkyū-buntansha) 服部 奈緒子  国立研究開発法人国立がん研究センター, 研究所, 研究員 (30611090)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
KeywordsDNA脱メチル化治療 / 効果予測マーカー / lncRNA
Outline of Final Research Achievements

DNA demethylation therapy is now expanding from hematological tumors to solid tumors. Previously, we have identified a long noncoding RNA, linc00162 (lnc162), as highly
and frequently expressed in gastric cancer cell lines sensitive to 5-aza-2′-deoxycytidine (5-aza-dC). Here, we aimed to reveal the molecular mechanisms how lnc162 is involved in 5-aza-dC sensitivity and the function of lnc162 in other solid tumors. In vivo experiments showed that lnc162
overexpression increased the sensitivity. Mechanistically, lnc162 interacted with an RNA splicing protein, HNRNPH1, and decreased splicing of an anti-apoptotic splicing variant, BCL-XL. In liposarcomas cell lines, lnc162 expression was induced by the treatment of 5-aza-dC, meaning that the involvement of lnc162 in 5-aza-dC sensitivity is universally applicable to solid tumors. lnc162 may have translational value to predict patients who will respond to 5-aza-dC. We have published these findings as an original paper.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、固形腫瘍へのDNA脱メチル化剤治療の効果予測マーカーであるlnc162が同定された。また、今回明らかとなった作用機序を考慮すると、lnc162を標的とすることによって、DNA脱メチル化剤を増強する治療戦略の開発につながる可能性もあることが示された。この研究成果によって、停滞している固形腫瘍へのDNA脱メチル化剤治療が促進すると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (13 results)

All 2021 2020 2019 2018

All Journal Article (7 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Influence of degree of DNA degradation in formalin-fixed and paraffin-embedded tissue samples on accuracy of genome-wide DNA methylation analysis2021

    • Author(s)
      Ueda S, Yamashita S, Watanabe S-i, Wakabayashi M, Motoi N, Noguchi M, Sekine S, Sato Y, Ushijima T.
    • Journal Title

      Epigenomics

      Volume: - Issue: 8 Pages: 565-576

    • DOI

      10.2217/epi-2020-0431

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic and epigenetic profiling indicates the proximal tubule origin of renal cancers in end‐stage renal disease2020

    • Author(s)
      Ishihara Hiroki、Yamashita Satoshi、Liu Yu‐Yu、Hattori Naoko、El‐Omar Omar、Ikeda Takashi、Fukuda Hironori、Yoshida Kazuhiko、Takagi Toshio、Taneda Sekiko、Kondo Tsunenori、Nagashima Yoji、Tanabe Kazunari、Ushijima Toshikazu
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 11 Pages: 4276-4287

    • DOI

      10.1111/cas.14633

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SAA1 is upregulated in gastric cancer-associated fibroblasts possibly by its enhancer activation2020

    • Author(s)
      Yasukawa Yoshimi、Hattori Naoko、Iida Naoko、Takeshima Hideyuki、Maeda Masahiro、Kiyono Tohru、Sekine Shigeki、Seto Yasuyuki、Ushijima Toshikazu
    • Journal Title

      Carcinogenesis

      Volume: 42 Issue: 2 Pages: 180-189

    • DOI

      10.1093/carcin/bgaa131

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] エピジェネティック変化2020

    • Author(s)
      牛島俊和
    • Journal Title

      入門腫瘍内科学 改訂第3版

      Volume: - Pages: 36-39

    • Related Report
      2020 Annual Research Report
  • [Journal Article] エピジェネティクス2020

    • Author(s)
      服部奈緒子、牛島俊和
    • Journal Title

      日本臨床 増刊号 「肉腫」

      Volume: 78 Pages: 95-102

    • NAID

      10018410248

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Distinct DNA methylation targets by aging and chronic inflammation: a pilot study using gastric mucosa infected with Helicobacter pylori2019

    • Author(s)
      Yamashita Satoshi, Nanjo Sohachi, Rehnberg Emil, Iida Naoko, Takeshima Hideyuki, Ando Takayuki, Maekita Takao, Sugiyama Toshiro, Ushijima Toshikazu
    • Journal Title

      Clinical Epigenetics

      Volume: 11 Issue: 1 Pages: 191-191

    • DOI

      10.1186/s13148-019-0789-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] LINC00162 Confers Sensitivity to 5-Aza-2'-deoxycytidine via Modulation of an RNA Splicing Protein, HNRNPH12019

    • Author(s)
      Zong Liang、Hattori Naoko、Yasukawa Yoshimi、Kimura Kana、Mori Akiko、Seto Yasuyuki、Ushijima Toshikazu
    • Journal Title

      Oncogene

      Volume: 印刷中 Issue: 26 Pages: 5281-5293

    • DOI

      10.1038/s41388-019-0792-8

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Low-dose DNA demethylating therapy induces reprogramming of specific cancer-related pathways at the single-cell level2021

    • Author(s)
      Takeshima Hideyuki、Yoda Yukie、Watanabe Naoko、Ushijima Toshikazu
    • Organizer
      第14回日本エピジェネティクス研究会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Epigenetic field: Discovery to A Clinical Application2019

    • Author(s)
      牛島俊和
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Identification of environmental factors that induce aberrant DNA methylation2019

    • Author(s)
      服部奈緒子、丹羽透、大河内(高田)江理子、今井俊夫、牛島俊和
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Gastric Cancer is Heavily Influenced by Aberrant DNA Methylation and Shows Sensitivity to DNA Demethylating Therapy2018

    • Author(s)
      牛島俊和、茂呂浩史、中村能章、服部奈緒子
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] LINC00162 Confers Sensitivity to 5-Aza-2’-deoxycytidine via Modulation of an RNA Splicing Protein, HNRNPH12018

    • Author(s)
      Yasukawa Y, Zong L, Hattori N, Mori A, Kimura K, Seto Y, Ushijima T
    • Organizer
      Post-A3 Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] LINC00162 Confers Sensitivity to 5-Aza-2’-deoxycytidine via Modulation of an RNA Splicing Protein, HNRNPH12018

    • Author(s)
      安川佳美、宗亮、服部奈緒子、瀬戸泰之、牛島俊和
    • Organizer
      第29回日本消化器癌発生学会総会
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi