Activation of RNA editing is a novel mechanism that promotes invasive potential of cancer-associated fibroblasts in colorectal cancer
Project/Area Number |
17K16557
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Digestive surgery
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Research Institution | Okayama University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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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)
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Keywords | RNA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.
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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。
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Report
(4 results)
Research Products
(7 results)
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[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.
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Journal Title
Cancer Lett
Volume: 444
Pages: 127-135
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
Int'l Joint Research
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[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
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[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
Int'l Joint Research
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