SET protein modulates H4 histone methylation status and regulates miR-137 level in oral squamous cell carcinoma

Epigenomics. 2020 Mar;12(6):475-485. doi: 10.2217/epi-2019-0181. Epub 2020 Apr 8.

Abstract

Aim: Histone acetylation and methylation control gene expression. We investigated the impact of SET knockdown on histone methylation status and the consequences for the miRNAs levels in oral squamous cell carcinoma (OSCC). Methods: OSCC cells with and without SET knockdown were analyzed by quantitative real-time PCR to determine miRNA levels, and by immunoreactions to histone modifications. Results: The knockdown of SET increased the levels of histone H4K20me2 and miR-137. Still, SET protein binds to the miR-137 promoter region. The transfection of miR-137 mimic reduced the KI67 and Rb proteins and proliferation of OSCC cells. Conclusion: Our results show for the first time a relationship between SET and histone methylation associated with the control of miRNA expression and KI67 and Rb as targets of miR-137 in OSCC.

Keywords: OSCC; SET/I2PP2A; histones; methylation; miR-137.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Neoplastic
  • Histone Chaperones / metabolism
  • Histone Chaperones / physiology*
  • Histones / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Ki-67 Antigen / metabolism
  • Methylation
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Retinoblastoma Protein / 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

  • DNA-Binding Proteins
  • Histone Chaperones
  • Histones
  • Hydroxamic Acids
  • Ki-67 Antigen
  • MIRN137 microRNA, human
  • MicroRNAs
  • Retinoblastoma Protein
  • SET protein, human
  • trichostatin A