Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
J Crohns Colitis. 2023 May 3;17(5):754-766. doi: 10.1093/ecco-jcc/jjac186.
Ulcerative colitis [UC] can lead to colitis-associated colorectal neoplasm [CAN]. Adenosine-to-inosine RNA editing, which is regulated by adenosine deaminase acting on RNA [ADAR], induces the post-transcriptional modification of critical oncogenes, including antizyme inhibitor 1 [AZIN1], leading to colorectal carcinogenesis. Therefore, we hypothesized that ADAR1 might be involved in the development of CAN in UC.
We systematically analysed a cohort of 139 UC cases [40 acute phase, 73 remission phase, 26 CAN]. The degree of inflammation was evaluated using the Mayo endoscopic score [MES].
The type 1 interferon [IFN]-related inflammation pathway was upregulated in the rectum of active UC, rectum of UC-CAN and tumour site of UC-CAN patients. ADAR1 expression was upregulated in the entire colon of CAN cases, while it was downregulated in non-CAN MES0 cases. ADAR1 expression in the rectum predicted the development of CAN better than p53 or β-catenin, with an area under the curve of 0.93. The high expression of ADAR1 and high AZIN1 RNA editing in UC was triggered by type 1 IFN stimulation from UC-specific microbiomes, such as seen in Fusobacterium in vitro analyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted by Fusobacterium, may induce carcinogenesis in UC.
The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC.
溃疡性结肠炎（UC）可导致结肠炎相关结直肠肿瘤（CAN）。由腺苷脱氨酶作用于 RNA（ADAR）调节的尿苷-肌苷 RNA 编辑，诱导关键癌基因的转录后修饰，包括抗酶抑制剂 1（AZIN1），导致结直肠发生癌变。因此，我们假设 ADAR1 可能参与 UC 中 CAN 的发生。
我们系统地分析了 139 例 UC 病例[40 例急性期，73 例缓解期，26 例 CAN]的队列。采用 Mayo 内镜评分（MES）评估炎症程度。
在活动期 UC 的直肠、UC-CAN 的直肠和 UC-CAN 患者的肿瘤部位，I 型干扰素（IFN）相关炎症通路上调。ADAR1 表达在 CAN 病例的整个结肠中上调，而在非 CAN-MES0 病例中下调。ADAR1 在直肠中的表达比 p53 或β-连环蛋白更好地预测 CAN 的发生，曲线下面积为 0.93。UC 中 ADAR1 的高表达和高 AZIN1 RNA 编辑是由 UC 特异性微生物组如 Fusobacterium 体外分析中 I 型 IFN 刺激触发的。ADAR1 表达促进 Fusobacterium 诱导 AZIN1 RNA 编辑，可能在 UC 中诱导癌变。
通过评估 MES0 UC 患者直肠中 ADAR1 的表达，可以评估 CAN 的风险，使 UC 患者免于不必要的结肠镜检查，减轻他们的身体负担。RNA 编辑可能参与 UC 的癌变过程，并可能用于促进 UC 中 CAN 的预防和治疗。
