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Activation of RNA editing is a novel mechanism that promotes invasive potential of cancer-associated fibroblasts in colorectal cancer

Research Project

Project/Area Number 17K16557
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionOkayama University

Principal Investigator

Shigeyasu Kunitoshi  岡山大学, 大学病院, 助教 (70544071)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
KeywordsRNA編集 / 大腸癌 / 微小環境 / 癌関連線維芽細胞 / ADAR1 / AZIN1 / RNA editing / 線維芽細胞 / 癌
Outline of Final Research Achievements

We systematically analyzed a large cohort of 627 colorectal cancer (CRC) specimens, and investigated the expression pattern of ADAR1 and the its biological significance on the antizyme inhibitor 1 (AZIN1) RNA editing levels. Both ADAR1 expression and AZIN1 RNA editing levels were significantly elevated in CRC tissues vs. normal mucosa, and these findings correlated with the increased expression of mesenchymal markers, Vimentin (ρ=0.44) and Fibroblast activation protein (ρ=0.38). Intriguingly, ADAR1 expression was specifically upregulated in both cancer cells and fibroblasts from cancerous lesions. Conditioned medium from cancer cells led to induction of ADAR1 expression and activation of AZIN1 RNA editing in fibroblasts (p<0.05). Additionally, edited AZIN1 enhanced the invasive potential of fibroblasts.

Academic Significance and Societal Importance of the Research Achievements

今回の研究の結果から大腸TME中のCAFのAZIN1発現の上昇は、CAFの浸潤能を増加させるとともに、腫瘍の浸潤能の重要な予測因子となり得ることが示された。
当研究は大腸癌TMEにおけるRNA編集の意義について検討した初めての独創的な研究であり、浸潤能を評価するバイオマーカーとなりうること、また新たな治療ターゲットとなりうることを示した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017

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

  • [Journal Article] Activation of AZIN1 RNA editing is a novel mechanism that promotes invasive potential of cancer-associated fibroblasts in colorectal cancer2019

    • Author(s)
      Takeda S, Shigeyasu K, Okugawa Y, Yoshida K, Mori Y, Yano S, Noma K, Umeda Y, Kondo Y, Kishimoto H, Teraishi F, Nagasaka T, Tazawa H, Kagawa S, Fujiwara T, Goel A.
    • Journal Title

      Cancer Lett

      Volume: 444 Pages: 127-135

    • DOI

      10.1016/j.canlet.2018.12.009

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Activation of AZIN1 RNA editing facilitates and promotes invasive potential of cancer associated fibroblasts in colorectal cancer2019

    • Author(s)
      Takeda S, Shigeyasu K, Okugawa Y, Yoshida K, Mori Y, Yano S, Noma K, Umeda Y, Kondo Y, Kishimoto H, Teraishi F, Takeshi N, Tazawa H, Kagawa S, Ajay G, Fujiwara T
    • Organizer
      AACR2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] AZIN1 RNA editing is a novel mechanism that enhances malignant potential of colorectal cancer microenvironment2019

    • Author(s)
      Takeda S, Shigeyasu K, Okugawa Y, Yoshida K, Mori Y, Yano S, Noma K, Umeda Y, Kondo Y, Kishimoto H, Teraishi F, Takeshi N, Tazawa H, Kagawa S, Ajay G, Fujiwara T
    • Organizer
      JCA2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Activation of AZIN1 RNA editing facilitates and promotes invasive potential of cancer associated fibroblasts in colorectal cancer2019

    • Author(s)
      Sho Takeda, Kunitoshi Shigeyasu, Yoshinaga Okugawa, Kazuhiro Yoshida, Yoshiko Mori, Shuya Yano, Kazuhiro Noma, Yuzo Umeda, Yoshitaka Kondo, Hiroyuki Kishimoto, Fuminori Teraishi, Hiroshi Tazawa, Shunsuke Kagawa, Ajay Goel, Toshiyoshi Fujiwara
    • Organizer
      AACR Annual Meeting 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel evidence for AZIN1 RNA editing-mediated oncogenic role in colorectal cancer2018

    • Author(s)
      Kunitoshi Shigeyasu, Ajay Goel, Toshiyoshi Fujiwara
    • Organizer
      JDDW 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 大腸癌における AZIN1 のRNA 編集に関する新しい知見2017

    • Author(s)
      重安 邦俊、武田 正、奥川 喜永、問山 裕二、永坂 岳司、田 澤 大、香川 俊輔、Ajay Goel、藤原 俊義
    • Organizer
      The 76th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2017 Research-status Report
  • [Presentation] Novel evidence for AZIN1 RNA editing-mediated oncogenic role in colorectal cancer2017

    • Author(s)
      Kunitoshi Shigeyasu, Shusuke Toden, Yoshinaga Okugawa, Jinsei Miyoshi, Takeshi Nagasaka, Toshiyoshi Fujiwara, Leilei Chen and Ajay Goel
    • Organizer
      AACR Annual Meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2022-03-04  

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