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miR-28 regulates the germinal center reaction and blocks tumor growth in preclinical models of non-Hodgkin lymphoma.
- Source :
-
Blood [Blood] 2017 Apr 27; Vol. 129 (17), pp. 2408-2419. Date of Electronic Publication: 2017 Feb 10. - Publication Year :
- 2017
-
Abstract
- Non-Hodgkin lymphoma comprises a variety of neoplasms, many of which arise from germinal center (GC)-experienced B cells. microRNA-28 (miR-28) is a GC-specific miRNA whose expression is lost in numerous mature B-cell neoplasms. Here we show that miR-28 regulates the GC reaction in primary B cells by impairing class switch recombination and memory B and plasma cell differentiation. Deep quantitative proteomics combined with transcriptome analysis identified miR-28 targets involved in cell-cycle and B-cell receptor signaling. Accordingly, we found that miR-28 expression diminished proliferation in primary and lymphoma cells in vitro. Importantly, miR-28 reexpression in human Burkitt (BL) and diffuse large B-cell lymphoma (DLBCL) xenografts blocked tumor growth, both when delivered in viral vectors or as synthetic, clinically amenable, molecules. Further, the antitumoral effect of miR-28 is conserved in a primary murine in vivo model of BL. Thus, miR-28 replacement is uncovered as a novel therapeutic strategy for DLBCL and BL treatment.<br /> (© 2017 by The American Society of Hematology.)
- Subjects :
- Animals
B-Lymphocytes pathology
Burkitt Lymphoma genetics
Burkitt Lymphoma immunology
Burkitt Lymphoma pathology
Cell Differentiation
Cell Proliferation
Genetic Vectors chemistry
Genetic Vectors metabolism
Germinal Center pathology
Humans
Immunoglobulin Class Switching
Immunologic Memory
Lentivirus genetics
Lentivirus metabolism
Lymphoma, Large B-Cell, Diffuse genetics
Lymphoma, Large B-Cell, Diffuse immunology
Lymphoma, Large B-Cell, Diffuse pathology
Mice
Mice, Inbred NOD
Mice, SCID
MicroRNAs immunology
Plasma Cells immunology
Plasma Cells pathology
Proteomics
Transcriptome
Transfection
Xenograft Model Antitumor Assays
B-Lymphocytes immunology
Burkitt Lymphoma therapy
Gene Expression Regulation, Neoplastic
Germinal Center immunology
Lymphoma, Large B-Cell, Diffuse therapy
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 129
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 28188132
- Full Text :
- https://doi.org/10.1182/blood-2016-08-731166