The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related genes and augments cell self-renewal

Virology. 2016 Dec:499:230-242. doi: 10.1016/j.virol.2016.09.020. Epub 2016 Sep 29.

Abstract

Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E2) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E2 on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E2 in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells.

Keywords: Cancer stem cells; Cervical cancer; HPV16 E7 oncoprotein; Human papillomaviruses; Oct3/4; Stemness-related genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Self Renewal*
  • Estradiol / metabolism
  • Female
  • Fibroblast Growth Factor 4 / genetics
  • Fibroblast Growth Factor 4 / metabolism
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / metabolism*
  • Humans
  • Mice
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism
  • Neoplastic Stem Cells / cytology*
  • Neoplastic Stem Cells / metabolism
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / metabolism*
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / physiopathology
  • Papillomavirus Infections / virology
  • SOXB1 Transcription Factors
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / physiopathology
  • Uterine Cervical Neoplasms / virology

Substances

  • FGF4 protein, human
  • Fibroblast Growth Factor 4
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Papillomavirus E7 Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • oncogene protein E7, Human papillomavirus type 16
  • Estradiol