SAHA inhibits the transcription initiation of HPV18 E6/E7 genes in HeLa cervical cancer cells

Gene. 2014 Dec 15;553(2):98-104. doi: 10.1016/j.gene.2014.10.007. Epub 2014 Oct 7.

Abstract

High risk human papillomavirus (HPV) is a well recognized causative agent of cervical cancer. Suberoylanilide hydroxamic acid (SAHA) is a potential anti-cervical cancer drug; however, its effect on the expression of HPV E6 and E7 genes remains unclear. Here, we show that, in SAHA treated HeLa cells, HPV18 E6 and E7 mRNA and protein levels were reduced, HPV18 promoter activity was decreased, and the association of RNP II with HPV18 promoter was diminished, suggesting that SAHA inhibited the transcription initiation of HPV18 E6 and E7 genes. In SAHA-treated HeLa, although the level of lysine 9-acetylated histone H3 in the whole cell extracts increased obviously, its enrichment on HPV18 promoter was significantly reduced which is correlated with the down-regulation of HPV E6 and E7.

Keywords: Cervical cancer; E6 and E7; Histone acetylation; Human papillomavirus; SAHA; Transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus / genetics*
  • Base Sequence
  • DNA Primers
  • DNA-Binding Proteins / genetics*
  • Female
  • Genes, Viral*
  • HeLa Cells
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Oncogene Proteins, Viral / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic / drug effects*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*
  • Vorinostat

Substances

  • DNA Primers
  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 18
  • E7 protein, Human papillomavirus type 18
  • Hydroxamic Acids
  • Oncogene Proteins, Viral
  • Vorinostat