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.

Differential regulation of miR-21 and miR-146a by Epstein-Barr virus-encoded EBNA2 / Rosato, Paola; Anastasiadou, Eleni; Garg, Neha; D., Lenze; Boccellato, Francesco; S., Vincenti; M., Severa; E. M., Coccia; Bigi, Rachele; Cirone, Mara; Ferretti, Elisabetta; Campese, Antonio Francesco; Hummel, M; Frati, Luigi; Presutti, Carlo; Faggioni, Alberto; Trivedi, Pankaj; First two authors equally, Contributed. - In: LEUKEMIA. - ISSN 0887-6924. - STAMPA. - 26:11(2012), pp. 2343-2352. [10.1038/leu.2012.108]

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

ROSATO, PAOLA;ANASTASIADOU, ELENI;GARG, NEHA;BOCCELLATO, FRANCESCO;BIGI, RACHELE;CIRONE, Mara;FERRETTI, ELISABETTA;CAMPESE, Antonio Francesco;FRATI, Luigi;PRESUTTI, Carlo;FAGGIONI, Alberto;TRIVEDI, PANKAJ;
2012

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.
2012
ebna2; mir-146a; mir-21; ebv; microrna; dlbcl
01 Pubblicazione su rivista::01a Articolo in rivista
Differential regulation of miR-21 and miR-146a by Epstein-Barr virus-encoded EBNA2 / Rosato, Paola; Anastasiadou, Eleni; Garg, Neha; D., Lenze; Boccellato, Francesco; S., Vincenti; M., Severa; E. M., Coccia; Bigi, Rachele; Cirone, Mara; Ferretti, Elisabetta; Campese, Antonio Francesco; Hummel, M; Frati, Luigi; Presutti, Carlo; Faggioni, Alberto; Trivedi, Pankaj; First two authors equally, Contributed. - In: LEUKEMIA. - ISSN 0887-6924. - STAMPA. - 26:11(2012), pp. 2343-2352. [10.1038/leu.2012.108]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/442623
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