Department of Gastroenterology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Endocrinol (Lausanne). 2024 Mar 7;15:1348216. doi: 10.3389/fendo.2024.1348216. eCollection 2024.
The pathogenesis of inflammatory bowel disease (IBD) remains unclear and is associated with an increased risk of developing colitis-associated cancer (CAC). Under sustained inflammatory stimulation in the intestines, loss of early DNA damage response genes can lead to tumor formation. Many proteins are involved in the pathways of DNA damage response and play critical roles in protecting genes from various potential damages that DNA may undergo. ERCC4 is a structure-specific endonuclease that participates in the nucleotide excision repair (NER) pathway. The catalytic site of ERCC4 determines the activity of NER and is an indispensable gene in the NER pathway. ERCC4 may be involved in the imbalanced process of DNA damage and repair in IBD-related inflammation and CAC. This article primarily reviews the function of ERCC4 in the DNA repair pathway and discusses its potential role in the processes of IBD-related inflammation and carcinogenesis. Finally, we explore how this knowledge may open novel avenues for the treatment of IBD and IBD-related cancer.
炎症性肠病（IBD）的发病机制尚不清楚，并且与发生结肠炎相关癌症（CAC）的风险增加有关。在肠道中持续的炎症刺激下，早期 DNA 损伤反应基因的丧失可导致肿瘤形成。许多蛋白质参与 DNA 损伤反应途径，在保护基因免受 DNA 可能经历的各种潜在损伤方面发挥着关键作用。ERCC4 是一种结构特异性内切酶，参与核苷酸切除修复（NER）途径。ERCC4 的催化位点决定了 NER 的活性，是 NER 途径中不可或缺的基因。ERCC4 可能参与 IBD 相关炎症和 CAC 中 DNA 损伤和修复的失衡过程。本文主要综述了 ERCC4 在 DNA 修复途径中的作用，并探讨了其在 IBD 相关炎症和癌变过程中的潜在作用。最后，我们探讨了这些知识如何为 IBD 和 IBD 相关癌症的治疗开辟新途径。
