CHD4 plays a critical role in arsenite-induced oxidative damage in human urothelial carcinoma

被引：3
|
作者：
Chang, Shu-Jyuan [1 ,2 ]
Bin, Pin-Jie [3 ]
Luo, Chi-Wen [4 ,5 ]
Chai, Chee-Yin [1 ,2 ,3 ,6 ]
机构：
[1] Kaohsiung Med Univ, Coll Med, Dept Pathol, Kaohsiung, Taiwan
[2] Kaohsiung Med Univ Hosp, Dept Pathol, Kaohsiung, Taiwan
[3] Kaohsiung Med Univ, Coll Med, Grad Inst Med, Kaohsiung, Taiwan
[4] Kaohsiung Med Univ Hosp, Dept Surg, Kaohsiung, Taiwan
[5] Kaohsiung Med Univ Hosp, Div Breast Surg, Dept Surg, Kaohsiung, Taiwan
[6] Natl Sun Yat Sen Univ Kaohsiung, Inst Biomed Sci, Kaohsiung, Taiwan
来源：
PATHOLOGY RESEARCH AND PRACTICE | 2022年 / 240卷
关键词：
Inorganic arsenic; Urothelial carcinoma; CHD4; Oxidative DNA repair; DNA methylation; CELL-CYCLE PROGRESSION; DNA; GENE;
D O I：
10.1016/j.prp.2022.154173
中图分类号：
R36 [病理学];
学科分类号：
100104 ;
摘要：
Inorganic arsenic (iAs), a known human carcinogen, induces oxidative DNA damage and epigenetic silencing of tumor suppressor genes related to tumor progression. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a chromatin remodeling protein that acts on DNA repair and DNA methylation under oxidative damage in malignancies, but the role of CHD4 in arsenical urothelial carcinoma (UC) is unidentified. Our purpose was to observe CHD4-related repair effects on As-stimulated oxidative damage in human UC. The markers of oxidative DNA damage 8-hydroxy-2'-deoxyguanosine (8-OHdG) and CHD4 were investigated by immunohistochemistry in 45 UC tissues from non-blackfoot disease (BFD) areas and BFD areas respectively. The cellular mechanisms of CHD4 involved in the oxidative DNA repair and DNA methylation were evaluated by immunocytochemistry and western blot. The expressions of CHD4 and 8-OHdG were significantly increased in UC patients from the Asexposed areas. The underlying mechanism of CHD4-mediated DNA repair and DNA methylation involved the activation of zinc finger MYND-type containing 8 (ZMYND8) and DNA methyltransferase (DNMTs) in SV-HUC-1, T24 and BFTC-905 cells. These results highlight the potential clinical significance of CHD4 in UCs from BFD areas. The CHD4-mediated oxidative DNA repair and epigenetic DNA methylation in UC cells stimulated by arsenic was revealed. CHD4 might be used as a prognostic indicator in arsenical UC.
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页数：7
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