Differential regulation of miR-21 and miR-146a by Epstein-Barr virus-encoded EBNA2

P. Rosato, E. Anastasiadou, N. Garg, D. Lenze, F. Boccellato, S. Vincenti, M. Severa, E. M. Coccia, R. Bigi, M. Cirone, E. Ferretti, A. F. Campese, M. Hummel, L. Frati, C. Presutti, A. Faggioni, P. Trivedi

Research output: Contribution to journalArticlepeer-review

Abstract

The discovery of microRNA (miR) represents a novel paradigm in RNA-based regulation of gene expression and their dysregulation has become a hallmark of many a tumor. In virally associated cancers, the host-pathogen interaction could involve alteration in miR expression. Epstein-Barr virus (EBV)-encoded EBNA2 is indispensable for the capacity of the virus to transform B cells in vitro. Here, we studied how it affects cellular miRs. Extensive miR profiling of the virus-infected and EBNA2-transfected B lymphoma cells revealed that oncomiR miR-21 is positively regulated by this viral protein. Conversely, Burkitts lymphoma (BL) cell lines infected with EBNA2 lacking P3HR1 strain did not show any increase in miR-21. EBNA2 increased phosphorylation of AKT and this was directly correlated with increased miR-21. In contrast, miR-146a was downregulated by EBNA2 in B lymphoma cells. Low miR-146a expression correlates with an elevated level of IRAK1 and type I interferon in EBNA2 transfectants. Taken together, the present data suggest that EBNA2 might contribute to EBV-induced B-cell transformation by altering miR expression and in particular by increasing oncomiR-like miR-21 and by affecting the antiviral responses of the innate immune system through downregulation of its key regulator miR-146a.

Original languageEnglish
Pages (from-to)2343-2352
Number of pages10
JournalLeukemia
Volume26
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • DLBCL
  • EBNA2
  • EBV
  • microRNA
  • miR-146a
  • miR-21

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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