Suppression of ELF4 in ulcerative colitis predisposes host to colorectal cancer

Hongqiang Du; Huawei Xia; Tongtong Liu; Yingjie Li; Jilong 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

doi:10.1016/j.isci.2021.102169

Suppression of ELF4 in ulcerative colitis predisposes host to colorectal cancer

Hongqiang Du, Huawei Xia, Tongtong Liu, Yingjie Li, Jilong 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

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”.

Original language	English
Article number	102169
Journal	iScience
Volume	24
Issue number	3
DOIs	https://doi.org/10.1016/j.isci.2021.102169
Publication status	Published - 19 Mar 2021
Externally published	Yes

Keywords

Biochemistry
Molecular Biology
Transcriptomics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2021.102169

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@article{ef30073d64744555944469ed8fc815fb,

title = "Suppression of ELF4 in ulcerative colitis predisposes host to colorectal cancer",

abstract = "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”.",

keywords = "Biochemistry, Molecular Biology, Transcriptomics",

author = "Hongqiang Du and Huawei Xia and Tongtong Liu and Yingjie Li and Jilong Liu and Bingteng Xie and Jingxuan Chen and Tong Liu and Lili Cao and Shengde Liu and Siji Li and Peiyan Wang and Dandan Wang and Zeming Zhang and Yunfei Li and Xiaohuan Guo and Aiwen Wu and Mo Li and Fuping You",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = mar,

day = "19",

doi = "10.1016/j.isci.2021.102169",

language = "English",

volume = "24",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - Suppression of ELF4 in ulcerative colitis predisposes host to colorectal cancer

AU - Du, Hongqiang

AU - Xia, Huawei

AU - Liu, Tongtong

AU - Li, Yingjie

AU - Liu, Jilong

AU - Xie, Bingteng

AU - Chen, Jingxuan

AU - Liu, Tong

AU - Cao, Lili

AU - Liu, Shengde

AU - Li, Siji

AU - Wang, Peiyan

AU - Wang, Dandan

AU - Zhang, Zeming

AU - Li, Yunfei

AU - Guo, Xiaohuan

AU - Wu, Aiwen

AU - Li, Mo

AU - You, Fuping

PY - 2021/3/19

Y1 - 2021/3/19

N2 - 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”.

AB - 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”.

KW - Biochemistry

KW - Molecular Biology

KW - Transcriptomics

UR - https://www.scopus.com/pages/publications/85101152136

U2 - 10.1016/j.isci.2021.102169

DO - 10.1016/j.isci.2021.102169

M3 - Article

AN - SCOPUS:85101152136

SN - 2589-0042

VL - 24

JO - iScience

JF - iScience

IS - 3

M1 - 102169

ER -

Suppression of ELF4 in ulcerative colitis predisposes host to colorectal cancer

Abstract

Keywords

UN SDGs

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