MiR-26a Mediates Ultraviolet B-Induced Apoptosis by Targeting Histone Methyltransferase EZH2 Depending on Myc Expression

Cell Physiol Biochem. 2017;43(3):1188-1197. doi: 10.1159/000481759. Epub 2017 Oct 5.

Abstract

Background/aims: Ultraviolet B (UVB) damage is the most essential etiological factor in skin carcinogenesis, and apoptosis leads to the efficient elimination of UVB-damaged cells. However, the mechanisms underlying resistance to UVB-induced apoptosis remain unclear.

Methods: HaCaT and A431 cells were used in the present study. Quantitative real-time PCR, single cell PCR, and western blotting were used to examine cancer-related gene expression at the mRNA and protein levels.

Results: We report that miR-26a, which is upregulated upon UVB irradiation, promotes UVB-induced apoptosis in HaCaT cells by targeting the histone methyltransferase EZH2. Moreover, the UVB/miR-26a/EZH2 regulatory axis largely depends on the MYC expression level. Interestingly, treatment with EZH2 inhibitors significantly enhanced UVB-induced apoptosis.

Conclusion: miR-26a/EZH2 might be potential targets for skin cancer prevention and therapy.

Keywords: Apoptosis; EZH2; MYC; MiR-26a; Skin cancer; UVB.

MeSH terms

  • 3' Untranslated Regions
  • Antagomirs / metabolism
  • Apoptosis / radiation effects*
  • Base Sequence
  • Cell Line
  • Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mutagenesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Sequence Alignment
  • Ultraviolet Rays*
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MIRN26A microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein