Suppression of ELF4 in ulcerative colitis predisposes host to colorectal cancer

作者：Hongqiang Du, Huawei Xia, Tongtong Liu, Yingjie Li, Ji‐Long Liu, Bingteng Xie, Jingxuan Chen, Tong Liu, Lili Cao, Shengde Liu, Siji Li, Peiyan Wang, Dandan Wang, Zeming Zhang, Yunfei Li, Xiaohuan Guo, Aiwen Wu, Mo Li, Fuping You · 发表于：iScience · 年份：2021 · DOI：10.1016/j.isci.2021.102169 · 被引用次数：25 · 研究领域：Inflammatory Bowel Disease、Helicobacter pylori-related gastroenterology studies、IL-33, ST2, and ILC Pathways

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, characterized by relapsing and remitting colon mucosal inflammation. For patients suffering from UC, a higher risk of colon cancer has been widely recognized. Here, we found that Elf4−/− mice developed colon tumors with 3 cycles of dextran sulfate sodium salt (DSS) treatment alone. We further showed that ELF4 suppression was prevalent in both patients with UC and DSS-induced mice models, and this suppression was caused by promoter region methylation. ELF4, upon PARylation by PARP1, transcriptionally regulated multiple DNA damage repair machinery components. Consistently, ELF4 deficiency leads to more severe DNA damage both in vitro and in vivo. Oral administration of montmorillonite powder can prevent the reduction of ELF4 in DSS-induced colitis models and lower the risk of colon tumor development during azoxymethane (AOM) and DSS induced colitis-associated cancer (CAC). These data provided additional mechanism of CAC initiation and supported the “epigenetic priming model of tumor initiation”.