RNA Editing is a Valuable Biomarker for Predicting Carcinogenesis in Ulcerative Colitis
RNA Editing is a Valuable Biomarker for Predicting Carcinogenesis in Ulcerative Colitis
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RNA 编辑是预测溃疡性结肠炎癌变的有价值的生物标志物
DOI：
10.1093/ecco-jcc/jjac186
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Noma K
中科院分区：
文献类型：
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作者：
Takahashi Kazutaka;Shigeyasu Kunitoshi;Kondo Yoshitaka;Gotoh Kazuyoshi;Yano Shuya;Umeda Yuzo;Inokuchi Toshihiro;Xu Caiming;Yoshida Kazuhiro;Umeda Hibiki;Takahashi Toshiaki;Takeda Sho;Yoshida Ryuichi;Teraishi Fuminori;Kishimoto Hiroyuki;Mori Yoshiko;Noma K
背景和目的溃疡性结肠炎（UC）可导致结肠炎相关性结直肠肿瘤（CAN）。由作用于RNA的腺苷脱氨酶[阿达尔]调节的腺苷至肌苷RNA编辑诱导关键癌基因（包括抗酶抑制剂1 [AZIN 1]）的转录后修饰，导致结直肠癌发生。因此，我们假设ADAR 1可能参与发展CAN在UC.MethodsWe系统地分析了一个队列的139例UC病例[40急性期，73缓解期，26 CAN]。使用马约内镜评分评价炎症程度[MES]. Results 1型干扰素[IFN]相关的炎症通路在活动性UC的直肠、UC-CAN的直肠和UC-CAN患者的肿瘤部位上调。ADAR 1在CAN病例的整个结肠中表达上调，而在非CAN MES 0病例中表达下调。直肠中的ADAR 1表达预测CAN的发展优于p53或β-catenin，曲线下面积为0.93。UC中ADAR 1的高表达和高AZIN 1 RNA编辑是由UC特异性微生物组的1型IFN刺激引发的，例如体外分析中在梭杆菌中观察到的。ADAR 1的表达是由梭杆菌促进的，ADAR 1对AZIN 1 RNA编辑的诱导可能会诱导UC的癌变。结论通过评估MES 0 UC患者直肠中ADAR 1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，并可用于促进UC中CAN的预防和治疗。
Background and AimsUlcerative 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.MethodsWe 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].ResultsThe 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 inFusobacterium in vitroanalyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted byFusobacterium, may induce carcinogenesis in UC.ConclusionsThe 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.