miR-28 regulates the germinal center reaction and blocks tumor growth in preclinical models of non-Hodgkin lymphoma
Nahikari Bartolomé-Izquierdo 1 , Virginia G de Yébenes 1 , Angel F Álvarez-Prado 1 , Sonia M Mur 1 , Juan A Lopez Del Olmo 2 , Sergio Roa 3 , Jesus Vazquez 2 4 , Almudena R Ramiro 1
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.
CITA DEL ARTÍCULO Blood. 2017 Apr 27;129(17):2408-2419. doi: 10.1182/blood-2016-08-731166. Epub 2017 Feb 10