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

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

Author information

1
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, SL9, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Electronic address: qyin@tulane.edu.
2
Department of Pathology and Laboratory Medicine, SL79, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Electronic address: xwang4@tulane.edu.
3
Department of Pathology and Laboratory Medicine, SL79, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Electronic address: cfewell@tulane.edu.
4
Department of Pathology and Laboratory Medicine, SL79, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Electronic address: erik@tulane.edu.
5
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, SL9, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Electronic address: jlasky@tulane.edu.

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

PMID:
27110708
PMCID:
PMC4884481
DOI:
10.1016/j.virol.2016.04.005
[Indexed for MEDLINE]
Free PMC Article

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