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Investigation of potential therapeutic strategies for esophageal squamous cell carcinoma focused on the functional modification of cancer stimulating RNA editing.

Research Project

Project/Area Number 18K07910
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKawasaki Medical School

Principal Investigator

MASUDA Kiyoshi  川崎医科大学, 医学部, 教授 (00457318)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsRNA編集 / RNA結合蛋白質 / 食道癌 / 食道扁平上皮癌 / 食道がん
Outline of Final Research Achievements

We found that ADAR1 was highly expressed in esophageal squamous cell carcinoma (ESCC). Knockdown of ADAR1 suppressed cell proliferation. Comprehensive analysis using microarrays suggested that ADAR1 may suppress the immune response and apoptosis and contribute to the survival of cancer cells. In ADAR1 knockdown cells, the binding between the target genes and cancer stimulating RBPs (csRBPs) were increased/decreased and then the amounts of mRNAs were altered. These results suggested that ADAR1 may cause A-to-I RNA editing in the 3’UTR of mRNAs that control cell growth, infiltration, and cancer immunity, and regulate association between csRBP and target mRNAs. In conclusion, ADAR1 may be a hub factor that induces disruption of the post-transcriptional regulatory mechanism in ESCC cells.

Academic Significance and Societal Importance of the Research Achievements

これまで、RNA編集異常の病態への関与は、神経変性疾患や精神疾患、一部の希少疾患で報告されているが、これらの分子機構は不明である。癌組織は正常組織に比べRNA編集活性が亢進しており、癌特異的なRNA編集パターンが見られることから、RNA編集不全と発癌との関連性が示唆されているが、癌特異的なRNA編集のほとんどが非翻訳領域に集中しており、機能予測が困難なことから、これらを直接結びつける分子機構の解明には至っていない。本研究結果は、食道癌におけるRBPが作る大きな機能モジュール内でのRNA編集の生物学的意義解明の端緒となる。

Report

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

    (8 results)

All 2021 2020 2019 2018

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

  • [Journal Article] Functionally confirmed compound heterozygous ADAM17 missense loss-of-function variants cause neonatal inflammatory skin and bowel disease 12021

    • Author(s)
      Imoto I, Saito M, Suga K, Kohmoto T, Otsu M, Horiuchi K, Nakayama H, Higashiyama S, Sugimoto M, Sasaki A, Homma Y, Shono M, Nakagawa R, Hayabuchi Y, Tange S, Kagami S, Masuda K
    • Journal Title

      Scientific reports

      Volume: 11 Issue: 1 Pages: 9552-9552

    • DOI

      10.1038/s41598-021-89063-0

    • NAID

      120007188413

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer2020

    • Author(s)
      Kohmoto T, Masuda K, Shoda K, Takahashi R, Ujiro S, Tange S, Ichikawa D, Otsuji E, Imoto I
    • Journal Title

      Gastric Cancer

      Volume: 23 Issue: 3 Pages: 403-417

    • DOI

      10.1007/s10120-019-01014-x

    • NAID

      40022220036

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Toll‐Like Receptor 9 Plays a Pivotal Role in Angiotensin II Induced Atherosclerosis2019

    • Author(s)
      Fukuda Daiju、Nishimoto Sachiko、Aini Kunduziayi、Tanaka Atsushi、Nishiguchi Tsuyoshi et al.
    • Journal Title

      Journal of the American Heart Association

      Volume: 8 Issue: 7

    • DOI

      10.1161/jaha.118.010860

    • NAID

      120006602927

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic significance of GAD1 overexpression in patients with resected lung adenocarcinoma2019

    • Author(s)
      Tsuboi M, Kondo K, Masuda K, Tange S, Kajiura K, Kohmoto T, Takizawa H, Imoto I, Tangoku A
    • Journal Title

      Cancer Medicine

      Volume: 8 Issue: 9 Pages: 4189-4199

    • DOI

      10.1002/cam4.2345

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel compound heterozygous CDH23 variants in a patient with Usher syndrome type I.2019

    • Author(s)
      Okano S, Makita Y, Katada A, Harabuchi Y, Kohmoto T, Naruto T, Masuda K, Imoto I.
    • Journal Title

      Hum Genome Var.

      Volume: 6 Issue: 1 Pages: 8-8

    • DOI

      10.1038/s41439-019-0037-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Primary microcephaly caused by novel compound heterozygous mutations in ASPM.2018

    • Author(s)
      Okamoto N, Kohmoto T, Naruto T, Masuda K, Imoto I.
    • Journal Title

      Hum Genome Var.

      Volume: 5 Issue: 1 Pages: 18015-18015

    • DOI

      10.1038/hgv.2018.15

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diverse roles of RNA-binding proteins in cancer traits and their implications in gastrointestinal cancers.2018

    • Author(s)
      Masuda K, Kuwano Y.
    • Journal Title

      Wiley Interdiscip Rev RNA.

      Volume: 10 Issue: 3

    • DOI

      10.1002/wrna.1520

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] KHSRP involved in esophageal squamous cell carcinoma progression by inducing the expression of a set of oncogenic miRNAs2019

    • Author(s)
      Masuda K, Kohmoto T, Imoto I
    • Organizer
      Cell Symposium: Regulatory RNAs
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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

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