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microRNA profiling in Epstein-Barr virus-associated B-cell lymphoma

Imig, Jochen ; Motsch, Natalie ; Zhu, Jia Yun ; Barth, Stephanie ; Okoniewski, Michal ; Reineke, Tanja ; Tinguely, Marianne ; Faggioni, Alberto ; Trivedi, Pankaj ; Meister, Gunter ; Renner, Christoph ; Grässer, Friedrich A.

In: Nucleic Acids Research, 2011, vol. 39, no. 5, p. 1880-1893

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    Title
    • microRNA profiling in Epstein-Barr virus-associated B-cell lymphoma
    Author
    • Imig, Jochen. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Motsch, Natalie. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Zhu, Jia Yun. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Barth, Stephanie. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Okoniewski, Michal. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Reineke, Tanja. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Tinguely, Marianne. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Faggioni, Alberto. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Trivedi, Pankaj. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Meister, Gunter. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Renner, Christoph. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    • Grässer, Friedrich A.. Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Center for integrated protein Sciences Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Munich, Germany, Functional Genomics Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, La Sapienza University, Rome, Italy, Regensburg University, Biochemistry I, Universitätstrasse 31, Regensburg, Germany and Division of Oncology, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Nucleic Acids Research, 2011, vol. 39, no. 5, p. 1880-1893. Oxford University Press
    Other Version
    Classification
    • Health
    Keywords
    OAI-PMH Identifier
    • oai:doc.rero.ch:294438
    Summary
    The Epstein-Barr virus (EBV) is an oncogenic human Herpes virus found in ∼15% of diffuse large B-cell lymphoma (DLBCL). EBV encodes miRNAs and induces changes in the cellular miRNA profile of infected cells. MiRNAs are small, non-coding RNAs of ∼19-26 nt which suppress protein synthesis by inducing translational arrest or mRNA degradation. Here, we report a comprehensive miRNA-profiling study and show that hsa-miR-424, -223, -199a-3p, -199a-5p, -27b, -378, -26b, -23a, -23b were upregulated and hsa-miR-155, -20b, -221, -151-3p, -222, -29b/c, -106a were downregulated more than 2-fold due to EBV-infection of DLBCL. All known EBV miRNAs with the exception of the BHRF1 cluster as well as EBV-miR-BART15 and -20 were present. A computational analysis indicated potential targets such as c-MYB, LATS2, c-SKI and SIAH1. We show that c-MYB is targeted by miR-155 and miR-424, that the tumor suppressor SIAH1 is targeted by miR-424, and that c-SKI is potentially regulated by miR-155. Downregulation of SIAH1 protein in DLBCL was demonstrated by immunohistochemistry. The inhibition of SIAH1 is in line with the notion that EBV impedes various pro-apoptotic pathways during tumorigenesis. The down-modulation of the oncogenic c-MYB protein, although counter-intuitive, might be explained by its tight regulation in developmental processes