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

•The DNA methylation of miR-155 CpG island regulates miR-155 expression in EBV-positive cells.•AP1 signaling pathway is involved in EBV-mediated miR-155 activation.•The regulation of miR-155 by EBV is dependent on more than one EBV gene or multiple cell signaling pathways.

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.