Methylation status and AP1 elements are involved in EBV-mediated miR-155 expression in EBV positive lymphoma cells.
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.
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.
Qinyan
Q
Yin
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.
Xia
X
Wang
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.
Claire
C
Roberts
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.
Erik K
EK
Flemington
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.
Joseph A
JA
Lasky
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000401:mortality* / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008223:Lymphoma / Q000209:etiology*; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
D019309:Epstein-Barr Virus Nuclear Antigens; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D018808:Transcription Factor AP-1
AP1; DNA methylation; EBNAs; EBV; Epstein Barr Virus; LMPs; MiR-155; MiRNA; MicroRNA; Pri-miR-155