Suppression of ELF4 in ulcerative colitis predisposes host to colorectal cancer

iScience

Fuping You¹  Jingxuan Chen²  Bingteng Xie³  Lili Cao⁴  Jilong Liu⁵  Aiwen Wu⁶  Huawei Xia⁷  Hongqiang Du⁷  Shengde Liu⁷  Zeming Zhang⁷  Tongtong Liu⁷  Yunfei Li⁷  Dandan Wang⁷  Xiaohuan Guo⁷  Tong Liu⁷  Peiyan Wang⁷  Siji Li⁷  Mo Li⁸  Yingjie Li⁸ 

[1] Corresponding author;Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100000, China;Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100000, China;College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163000, China;Department of surgical oncology, ChuiYangLiu Hospital affiliated to Tsinghua University, Beijing 100000, China;Institute of Immunology, Tsinghua University School of Medicine, Beijing 100000, China;Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing 100000, China;Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100000, China;

关键词: Biochemistry;    Molecular Biology;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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”.

【 授权许可】

Unknown