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标题：Suppression of ELF4 in ulcerative colitis predisposes host to colorectal cancer
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作者：Hongqiang Du ; Huawei Xia ; Tongtong Liu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：3
页码：1-52
DOI：10.1016/j.isci.2021.102169
语种：English
出版社：Elsevier
摘要：SummaryUlcerative 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 thatElf4−/−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 bothin vitroandin 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”.Graphical abstractDisplay OmittedHighlights•Elf4 expression is suppressed in both colitis and colitis-associated cancer (CAC).•Elf4 deficiency leads to increased hyper-susceptibility to colitis and CAC in mice•Elf4 promotes DNA damage repair upon PARylation by PARP1•Oral administration of montmorillonite lowers risk of CAC developmentBiochemistry; Molecular Biology; Transcriptomics