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

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, Burkitt's 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.
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P. Rosato, E. Anastasiadou, N. Garg, D. Lenze, F. Boccellato, et al.. Differential regulation of miR-21 and miR-146a by Epstein-Barr virus-encoded EBNA2.. Leukemia, Nature Publishing Group: Open Access Hybrid Model Option B, 2012, 26 (11), pp.2343-52. ⟨10.1038/leu.2012.108⟩. ⟨pasteur-00955406⟩

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