The 19q13 KRAB Zinc-finger protein ZFP82 suppresses the growth and invasion of esophageal carcinoma cells through inhibiting NF-κB transcription and inducing apoptosis

Epigenomics. 2019 Jan;11(1):65-80. doi: 10.2217/epi-2018-0092. Epub 2018 Sep 13.

Abstract

Aim: To study the epigenetic alternations and biological functions of ZFP82 in esophageal squamous cell carcinoma.

Materials & methods: Analysis of ZFP82 expression was carried out by quantitative real-time PCR. Cell function was tested by MTS cell proliferation assay, transwell assay and flow cytometry. Gene mechanisms were studied by reverse transcription-PCR (RT-PCR), quantitative real-time PCR, luciferase reporter assay and Western blot.

Results: ZFP82 promoter methylation was downregulated in esophageal squamous cell carcinoma. ZFP82 ectopic expression suppressed cell function and regulated NF-κB phosphorylation and genes involved in cell cycle arrest and apoptosis. Moreover, ZFP82 methylation was correlated with age, tumor stage and outcome.

Conclusion: ZFP82 is a tumor suppressor and is disrupted by promoter CpG methylation during esophageal carcinogenesis.

Keywords: CpG methylation; ESCC; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics*
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chromosomes, Human, Pair 19*
  • DNA Methylation
  • Ectopic Gene Expression
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Neoplasm Metastasis
  • Nuclear Proteins / genetics*
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Binding
  • Transcription, Genetic
  • Tumor Burden

Substances

  • NF-kappa B
  • Nuclear Proteins
  • ZFP82 protein, human