Benzene and its metabolite decreases cell proliferation via LncRNA-OBFC2A-mediated anti-proliferation effect involving NOTCH1 and KLF15

Oncotarget. 2017 Jun 20;8(25):40857-40871. doi: 10.18632/oncotarget.16588.

Abstract

LncRNA has been considered to play a crucial role in the progression of several diseases by affecting cell proliferation. However, its role in benzene toxicity remains unclear. Our study showed that the expression of lncRNA-OBFC2A increased accompanied with the change of cell proliferation related-genes in benzene-exposed workers. In vitro experiments, 1,4-Benzoquinone dose-dependently inhibited cell proliferation and simultaneously caused the decrease of NOTCH1 expression and the increase of KLF15 in AHH-1 cell lines. Meanwhile, 1, 4-Benzoquinone obviously increased the expression of lncRNA-OBFC2A, which was consistent with our previous population results. Therefore, we propose that lncRNA-OBFC2A is involved in benzene toxicity by regulating cell proliferation. Further, we successfully constructed a lentivirus model of interfering the expression of lncRNA-OBFC2A. After interfering lncRNA-OBFC2A, the cell proliferation inhibition and the expression of NOTCH1 and KLF15 induced by 1, 4-Benzoquinone were reversed. Subsequently, RNA fluorescence in situ Hybridization assay showed that lncRNA-OBFC2A was located in cell nuclei. These results suggest that benzene and its metabolite decreases cell proliferation via LncRNA-OBFC2A-mediated anti-proliferation effect involving NOTCH1 and KLF15. LncRNA-OBFC2A can be a potential biomarker for benzene toxicity.

Keywords: 1; 4-Benzoquinone; RNA fluorescence in situ Hybridization assay; cell proliferation; lncRNA.

MeSH terms

  • Benzene / poisoning*
  • Benzoquinones / poisoning
  • Biomarkers / analysis
  • Case-Control Studies
  • Cell Proliferation / drug effects
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Nuclear Proteins / genetics*
  • Occupational Diseases / blood
  • Occupational Diseases / chemically induced
  • Occupational Diseases / genetics
  • Occupational Diseases / pathology
  • Occupational Exposure
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics*
  • Receptor, Notch1 / genetics*
  • Transfection

Substances

  • Benzoquinones
  • Biomarkers
  • KLF15 protein, human
  • Kruppel-Like Transcription Factors
  • NOTCH1 protein, human
  • Nuclear Proteins
  • RNA, Long Noncoding
  • Receptor, Notch1
  • Benzene