COPA A-to-I RNA editing hijacks endoplasmic reticulum stress to promote metastasis in colorectal cancer
COPA A-to-I RNA editing hijacks endoplasmic reticulum stress to promote metastasis in colorectal cancer
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COPA A-to-I RNA 编辑劫持内质网应激促进结直肠癌转移
DOI：
10.1016/j.canlet.2022.215995
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发表时间：
2022
期刊：
影响因子：
9.7
通讯作者：
Ya-ping Ye
中科院分区：
文献类型：
--
作者：
Shu-yang Wang;Ling-jie Zhang;Guo-jun Chen;Qi-qi Ni;Yuan Huang;Dan Zhang;Fang-yi Han;Wen-feng He;Li-ling He;Yan-qing Ding;Hong-li Jiao;Ya-ping Ye
RNA编辑是用于产生氨基酸变化的最常见的RNA水平修饰之一。我们鉴定了CRC转移中的COPA A至I RNA编辑事件。我们的研究结果表明，COPA A-to-I RNA编辑率在转移性CRC组织中显著增加，并且与T和N期的侵袭性肿瘤密切相关。COPA I164 V蛋白破坏Golgi-ER逆向转运功能，诱导ER应激，促进转录因子ATF 6、XBP 1和ATF 4向细胞核转位，激活MALAT 1、MET、ZEB 1的表达，导致CRC细胞浸润和转移。此外，COPA A-to-I RNA编辑率与免疫浸润评分呈正相关。总的来说，COPA I164 V蛋白劫持了ER应激以促进CRC的转移，并且COPA A-to-I RNA编辑率可能是患者对免疫检查点抑制剂（ICI）治疗反应的潜在预测因子。
RNA editing is among the most common RNA level modifications for generating amino acid changes. We identified a COPA A-to-I RNA editing event in CRC metastasis. Our results showed that the COPA A-to-I RNA editing rate was significantly increased in metastatic CRC tissues and was closely associated with aggressive tumors in the T and N stages. The COPA I164V protein damaged the Golgi–ER reverse transport function, induced ER stress, promoted the translocation of the transcription factors ATF6, XBP1 and ATF4 into the nucleus, and activated the expression of MALAT1, MET, ZEB1, and lead to CRC cell invasion and metastasis. Moreover, the COPA A-to-I RNA editing rate was positively correlated with the immune infiltration score. Collectively, the COPA I164V protein hijacked ER stress to promote the metastasis of CRC, and the COPA A-to-I RNA editing rate may be a potential predictor for patient response to immune checkpoint inhibitor (ICIs) treatment.