miR-217 is an oncogene that enhances the germinal center reaction
| Autor: | Marta Cañamero, Rubén Nogales-Cadenas, Almudena R. Ramiro, Nahikari Bartolomé-Izquierdo, Virginia G. de Yébenes, Miguel A. Piris, Nerea Martinez, Lorena Di Lisio, Pablo Pérez-Durán, Sonia M. Mur, Davide F. Robbiani, Alberto Pascual-Montano |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Immunoglobulin gene
medicine.medical_specialty DNA Repair Lymphoma Transgene Immunology Somatic hypermutation Mice Transgenic Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Inside BLOOD Commentary Gene expression microRNA medicine Animals Gene Regulatory Networks Gene Cells Cultured 030304 developmental biology 0303 health sciences B-Lymphocytes Oncogene business.industry Germinal center Cell Biology Hematology Oncogenes Germinal Center Microarray Analysis 3. Good health Cell biology Surgery MicroRNAs Cell Transformation Neoplastic 030220 oncology & carcinogenesis Proto-Oncogene Proteins c-bcl-6 business DNA Damage |
| Zdroj: | Blood |
| ISSN: | 0006-4971 |
| DOI: | 10.1182/blood-2013-12-543611 |
| Popis: | microRNAs are a class of regulators of gene expression that have been shown critical for a great number of biological processes; however, little is known of their role in germinal center (GC) B cells. Although the GC reaction is crucial to ensure a competent immune response, GC B cells are also the origin of most human lymphomas, presumably due to bystander effects of the immunoglobulin gene remodeling that takes place at these sites. Here we report that miR-217 is specifically upregulated in GC B cells. Gain- and loss-of-function mouse models reveal that miR-217 is a positive modulator of the GC response that increases the generation of class-switched antibodies and the frequency of somatic hypermutation. We find that miR-217 down-regulates the expression of a DNA damage response and repair gene network and in turn stabilizes Bcl-6 expression in GC B cells. Importantly, miR-217 overexpression also promotes mature B-cell lymphomagenesis; this is physiologically relevant as we find that miR-217 is overexpressed in aggressive human B-cell lymphomas. Therefore, miR-217 provides a novel molecular link between the normal GC response and B-cell transformation. |
| Databáze: | OpenAIRE |
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