1. Differential regulation of miR-21 and miR-146a by Epstein-Barr virus-encoded EBNA2
- Author
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Rosato, Paola, Anastasiadou, Eleni, Garg, Neha, Lenze, D., Boccellato, Francesco, Vincenti, S., Severa, M., Coccia, E. M., Bigi, Rachele, Cirone, Mara, Ferretti, Elisabetta, Campese, Antonio Francesco, Hummel, M, Frati, Luigi, Presutti, Carlo, Faggioni, Alberto, Trivedi, Pankaj, First two authors equally contributed, Department of Experimental Medicine [Roma], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Genetics and Molecular Biology, Department of Infectious, Parasitic and Immune-Mediated Diseases [Rome], and Istituto Superiore di Sanita [Rome]
- Subjects
Cancer Research ,Herpesvirus 4, Human ,viruses ,medicine.disease_cause ,0302 clinical medicine ,Interferon ,immune system diseases ,hemic and lymphatic diseases ,Regulation of gene expression ,0303 health sciences ,ebna2 ,mir-146a ,mir-21 ,ebv ,microrna ,dlbcl ,microRNA ,IRAK1 ,Hematology ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Original Article ,miR-21 ,MESH: Epstein-Barr Virus Nuclear Antigens ,medicine.drug ,MESH: Cell Line, Tumor ,Blotting, Western ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Virus ,03 medical and health sciences ,Viral Proteins ,Downregulation and upregulation ,EBV ,Cell Line, Tumor ,medicine ,MESH: Blotting, Northern ,MESH: Blotting, Western ,Humans ,030304 developmental biology ,EBNA2 ,MESH: Humans ,MESH: Herpesvirus 4, Human ,Oncomir ,Blotting, Northern ,Epstein–Barr virus ,Molecular biology ,MESH: Gene Knockdown Techniques ,MESH: Viral Proteins ,miR-146a ,MicroRNAs ,Epstein-Barr Virus Nuclear Antigens ,DLBCL ,Cancer research ,MESH: MicroRNAs - Abstract
International audience; 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.
- Published
- 2012
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