Methylation status and AP1 elements are involved in EBV-mediated miR-155 expression in EBV positive lymphoma cells

Virology. 2016 Jul;494:158-67. doi: 10.1016/j.virol.2016.04.005. Epub 2016 Apr 26.

Abstract

The relationship between Epstein Barr Virus (EBV) and miR-155 is well established. EBV infection induces miR-155 expression, which is expressed at higher levels in EBV latency type III cells compared to EBV latency type I cells. However, the mechanism by which EBV latency genes activate miR-155 expression is still unclear. Here we present data showing that DNA methylation regulates miR-155 expression. We also provide evidence that the AP1 signaling pathway is involved in EBV-mediated miR-155 activation, and that Bay11 influences signaling of the miR-155 promoter AP1 element. Lastly, we show that LMP2A, LMP1 and EBNAs cannot activate miR-155 expression alone, indicating that the regulation of miR-155 by EBV is dependent on more than one EBV gene or cell signaling pathway. We conclude that the regulation of miR-155 in EBV-positive cells occurs through multiple cell signaling processes involving EBV-mediated chromatin remodeling, cell signaling regulation and transcription factor activation.

Keywords: AP1; DNA methylation; EBNAs; EBV; Epstein Barr Virus; LMPs; MiR-155; MiRNA; MicroRNA; Pri-miR-155.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line
  • CpG Islands
  • DNA Methylation*
  • Epstein-Barr Virus Infections / genetics*
  • Epstein-Barr Virus Infections / mortality*
  • Epstein-Barr Virus Infections / virology
  • Epstein-Barr Virus Nuclear Antigens / genetics
  • Epstein-Barr Virus Nuclear Antigens / metabolism
  • Gene Expression Regulation
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Lymphoma / etiology*
  • MicroRNAs / genetics*
  • Models, Biological
  • Promoter Regions, Genetic
  • Protein Binding
  • Response Elements*
  • Signal Transduction
  • Transcription Factor AP-1 / metabolism

Substances

  • Epstein-Barr Virus Nuclear Antigens
  • MIRN155 microRNA, human
  • MicroRNAs
  • Transcription Factor AP-1