Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, China.
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, China.
Cancer Lett. 2023 Jan 28;553:215995. doi: 10.1016/j.canlet.2022.215995. Epub 2022 Nov 4.
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.
RNA 编辑是在产生氨基酸变化的 RNA 水平修饰中最常见的一种。我们在 CRC 转移中发现了 COPA A-to-I RNA 编辑事件。我们的结果表明，转移性 CRC 组织中的 COPA A-to-I RNA 编辑率显著增加，并且与 T 期和 N 期侵袭性肿瘤密切相关。COPA I164V 蛋白破坏了高尔基体-内质网逆向转运功能，诱导内质网应激，促进转录因子 ATF6、XBP1 和 ATF4 转位入核，并激活 MALAT1、MET、ZEB1 的表达，导致 CRC 细胞侵袭和转移。此外，COPA A-to-I RNA 编辑率与免疫浸润评分呈正相关。综上所述，COPA I164V 蛋白劫持内质网应激以促进 CRC 的转移，而 COPA A-to-I RNA 编辑率可能是预测患者对免疫检查点抑制剂（ICIs）治疗反应的潜在指标。
