title: 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.
authors.affiliation: Department of Experimental Medicine, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Rosato
authors.forename: E
authors.initials: E
authors.lastname: Anastasiadou
authors.forename: N
authors.initials: N
authors.lastname: Garg
authors.forename: D
authors.initials: D
authors.lastname: Lenze
authors.forename: F
authors.initials: F
authors.lastname: Boccellato
authors.forename: S
authors.initials: S
authors.lastname: Vincenti
authors.forename: M
authors.initials: M
authors.lastname: Severa
authors.forename: E M
authors.initials: EM
authors.lastname: Coccia
authors.forename: R
authors.initials: R
authors.lastname: Bigi
authors.forename: M
authors.initials: M
authors.lastname: Cirone
authors.forename: E
authors.initials: E
authors.lastname: Ferretti
authors.forename: A F
authors.initials: AF
authors.lastname: Campese
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: L
authors.initials: L
authors.lastname: Frati
authors.forename: C
authors.initials: C
authors.lastname: Presutti
authors.forename: A
authors.initials: A
authors.lastname: Faggioni
authors.forename: P
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; C542542:MIRN146 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D014764:Viral Proteins