Publicaciones científicas

miR-28 regulates the germinal center reaction and blocks tumor growth in preclinical models of non-Hodgkin lymphoma

17-abr-2017 | Revista: Blood

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