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

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Shu-Jyuan Chang1, Pin-Jie Bin2, Chi-Wen Luo3

  • 1Department of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Pathology, Research and Practice
|October 28, 2022
PubMed

Insights

Chromodomain-helicase-DNA-binding protein 4 (CHD4) plays a key role in repairing arsenic-induced DNA damage and regulating epigenetic changes in urothelial carcinoma (UC). Increased CHD4 expression is linked to arsenic exposure and may serve as a prognostic indicator for this cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Environmental Health

Background:

  • Inorganic arsenic (iAs) is a human carcinogen causing oxidative DNA damage and epigenetic alterations.
  • Chromodomain-helicase-DNA-binding protein 4 (CHD4) is involved in DNA repair and methylation under oxidative stress.
  • The role of CHD4 in arsenical urothelial carcinoma (UC) remains unclear.

Purpose of the Study:

  • To investigate CHD4's role in arsenic-induced oxidative DNA damage and repair mechanisms in human UC.
  • To explore the clinical significance of CHD4 in UC patients from arsenic-exposed regions.

Main Methods:

  • Immunohistochemistry was used to assess CHD4 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression in 45 UC tissues.
  • Immunocytochemistry and Western blot analyzed cellular mechanisms of CHD4 in DNA repair and methylation.
  • Cell lines (SV-HUC-1, T24, BFTC-905) were used to study arsenic-stimulated effects.

Main Results:

  • CHD4 and 8-OHdG expression were significantly elevated in UC patients from arsenic-exposed areas.
  • CHD4-mediated DNA repair and methylation involved the activation of ZMYND8 and DNMTs.
  • These findings reveal CHD4's involvement in arsenic-induced oxidative DNA damage and epigenetic modifications in UC cells.

Conclusions:

  • CHD4 is implicated in the oxidative DNA repair and epigenetic DNA methylation processes in arsenic-stimulated UC cells.
  • CHD4 may hold potential as a prognostic biomarker for arsenical urothelial carcinoma, particularly in Blackfoot Disease endemic areas.
Keywords:
CHD4DNA methylationInorganic arsenicOxidative DNA repairUrothelial carcinoma

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