Repression of DOK7 mediated by DNMT3A promotes the proliferation and invasion of KYSE410 and TE-12 ESCC cells

Biomed Pharmacother. 2017 Jun:90:93-99. doi: 10.1016/j.biopha.2017.02.111. Epub 2017 Mar 24.

Abstract

Increasing evidence shows that aberrant epigenetic regulation of tumor suppressor genes is a contributing factor to their altered expression in esophageal squamous cell carcinoma (ESCC). In the current study, we investigate the role of DOK7 in ESCC cells. We found that enforced expression of DOK7 inhibited the proliferation and invasion of ESCC cells. We also found that treatment of ESCC cells with the DNA methylation inhibitor, 5-aza-2-deoxycytidine (5-azadC), induced the demethylation of DOK7 in promoter and DOK7 expression. Moreover, silencing DNMT3A decreased methylation of DOK7 and increased DOK7 expression, followed by repressing the proliferation and invasion of ESCC cells. Collectively, our data indicated that silencing DNMT3A inhibits proliferation and invasion in ESCC cells by inducing demethylation of DOK7.

Keywords: DNMT3A; DOK7; Esophageal squamous cell carcinoma.

MeSH terms

  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Carcinoma, Squamous Cell / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • DNA Methyltransferase 3A
  • Decitabine
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / genetics
  • Esophageal Neoplasms / genetics
  • Esophageal Squamous Cell Carcinoma
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Silencing / drug effects
  • Gene Silencing / physiology
  • Humans
  • Muscle Proteins / genetics*
  • Neoplasm Invasiveness / genetics*
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics

Substances

  • DNMT3A protein, human
  • DOK7 protein, human
  • Muscle Proteins
  • Decitabine
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • Azacitidine