Effect of Hypoxia on Proliferation and the Expression of the Genes HIF-1α and JMJD1A in Head and Neck Squamous Cell Carcinoma Cell Lines

Anticancer Res. 2021 Jan;41(1):113-122. doi: 10.21873/anticanres.14756.

Abstract

Background/aim: The aim of the study was to investigate the effects of hypoxia on proliferation and the expression of HIF-1α (hypoxia-inducible factor 1 alpha) and JMJD1A (jumonji domain 1A) in head and neck squamous cell carcinoma (HNSCC).

Materials and methods: FaDu and HLaC78 cells were incubated for 1-24 h in hypoxia and normoxia. Cell proliferation, mRNA and protein levels of HIF-1α and JMJD1A were quantified by counting, PCR and western blot.

Results: Hypoxia led to a constant decrease in cell proliferation. Short hypoxia resulted in an increase in HIF-1α mRNA levels. This effect was reversed after longer incubation. The western blot for HIF-1α showed a maximum accumulation after 3-6 h of hypoxia. In FaDu cells, the concentration of JMJD1A reached a peak after 6 h and decreased thereafter, whereas in HLaC78 cells, it presented a second peak after 48 h.

Conclusion: The transcription factors HIF-1α and JMJDA1 were confirmed as relevant hypoxia-dependent regulators of carcinogenesis in HNSCC.

Keywords: FaDu; HIF-1α; HLaC78; Head and neck squamous cell carcinoma (HNSCC); JMJD1A; hypoxia; proliferation.

MeSH terms

  • Cell Hypoxia / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoxia / genetics*
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Jumonji Domain-Containing Histone Demethylases
  • KDM3A protein, human