title: Epstein-Barr virus infection induces miR-21 in terminally differentiated malignant B cells.
abstract: The association of Epstein-Barr virus (EBV) with plasmacytoid malignancies is now well established but how the virus influences microRNA expression in such cells is not known. We have used multiple myeloma (MM) cell lines to address this issue and find that an oncomiR, miR-21 is induced after in vitro EBV infection. The PU.1 binding site in miR-21 promoter was essential for its activation by the virus. In accordance with its noted oncogenic functions, miR-21 induction in EBV infected MM cells caused downregulation of p21 and an increase in cyclin D3 expression. EBV infected MM cells were highly tumorigenic in SCID mice. Given the importance of miR-21 in plasmacytoid malignancies, our findings that EBV could further exacerbate the disease by inducing miR-21 has interesting implications both in terms of diagnosis and future miR based therapeutical approaches for the virus associated plasmacytoid tumors.
authors.affiliation: Department of Experimental Medicine, La Sapienza University, Rome, Italy.
authors.forename: Eleni
authors.initials: E
authors.lastname: Anastasiadou
authors.affiliation: Department of Molecular Medicine, La Sapienza University, Rome, Italy.
authors.forename: Neha
authors.initials: N
authors.lastname: Garg
authors.affiliation: Department of Experimental Medicine, La Sapienza University, Rome, Italy.
authors.forename: Rachele
authors.initials: R
authors.lastname: Bigi
authors.affiliation: Department of Experimental Medicine, La Sapienza University, Rome, Italy.
authors.forename: Shivangi
authors.initials: S
authors.lastname: Yadav
authors.affiliation: Department of Molecular Medicine, La Sapienza University, Rome, Italy.
authors.forename: Antonio Francesco
authors.initials: AF
authors.lastname: Campese
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Lapenta
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Spada
authors.affiliation: Department of Clinical Pathology, San Filippo Neri Hospital, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cuomo
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Botta
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.affiliation: Department of Experimental Medicine, La Sapienza University, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.affiliation: Department of Molecular Medicine, La Sapienza University, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
authors.affiliation: Department of Experimental Medicine, La Sapienza University, Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Faggioni
authors.affiliation: Department of Experimental Medicine, La Sapienza University, Rome, Italy.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D056743:Cyclin D3 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000235:genetics*; D004854:Herpesvirus 4, Human; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D009101:Multiple Myeloma / Q000235:genetics / Q000821:virology; D011401:Promoter Regions, Genetic
chemical_list: D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs
keywords: EBV; miR-21; multiple myeloma; plasma cells