Establishment of a new innovative treatment strategy for uterine carcinosarcoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09753
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Okayama University
• Principal Investigator: KEIICHIRO NAKAMURA 岡山大学, 医歯薬学域, 准教授 (90359886)
• Co-Investigator(Kenkyū-buntansha): 増山 寿 岡山大学, 医歯薬学域, 教授 (30314678) ; 小川 千加子 岡山大学, 大学病院, 講師 (50583035) ; 松原 侑子 岡山大学, 医歯薬学総合研究科, 非常勤研究員 (50835139) ; 松岡 敬典 岡山大学, 大学病院, 助教 (60835057)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 子宮体部癌肉腫 / RNA編集

Outline of Final Research Achievements

Adenosine-to-inosine (A-to-I) RNA editing is a recently described epigenetic modification, which is believed to constitute a key oncogenic mechanism in human cancers. ADAR1 showed significant association with worse histology, and lymph vascular space involvementin EC. The level of AZIN1 RNA editing was also significantly associated with worse histology. ADAR1 expression was significantly correlated with AZIN1 RNA editing level. Multivariate analysis indicated that higher ADAR1 expression along with AZIN1 RNA editing is an independent predictor of prognosis in EC patients. Knockdown of ADAR1 led to increased MDA-5, RIG-I, PKR, and IRF-7 expression, which in turn resulted in increased levels of Bak and apoptosis in EC cells. High ADAR1 expression along with AZIN1 RNA editing could be a predictor of worse prognosis in EC. ADAR1 could be a potential therapeutic target in EC patients.

Free Research Field

婦人科

Academic Significance and Societal Importance of the Research Achievements

子宮体癌症例を解析した結果，ADAR1およびantizyme inhibitor 1（AZIN1）の発現レベル上昇は組織型に関連しており，ADAR1とAZIN1 RNAレベルがいずれも上昇していた症例は予後不良であった。 ADAR1 ノックダウンによりインターフェロン経路に作用し，Bakとアポトーシスが増加を認め，当研究は子宮体癌における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，子宮体癌バイオマーカーとなりうることだけでなく，新たな治療ターゲットとなりうることを示し,癌肉腫に特に有効なことが認められた。