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

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16557
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Okayama 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
• Keywords: RNA編集 / 大腸癌 / 微小環境 / 癌関連線維芽細胞 / ADAR1 / AZIN1

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.

Free Research Field

エピジェネティクス

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。