Fuertes, TeresaÁlvarez-Corrales, EmigdioGómez-Escolar, CarmenUbieto-Capella, PatriciaSerrano-Navarro, Álvarode Molina, AntonioMéndez, JuanRamiro, Almudena Rde Yébenes, Virginia G2023-12-112023-12-112023-10-18Cell Death Dis. 2023 Oct 18;14(10):687.http://hdl.handle.net/20.500.12105/16761Diffuse large B cell lymphoma (DLBCL) is the most common aggressive B cell lymphoma and accounts for nearly 40% of cases of B cell non-Hodgkin lymphoma. DLBCL is generally treated with R-CHOP chemotherapy, but many patients do not respond or relapse after treatment. Here, we analyzed the therapeutic potential of the tumor suppressor microRNA-28 (miR-28) for DLBCL, alone and in combination with the Bruton's tyrosine kinase inhibitor ibrutinib. Combination therapy with miR-28 plus ibrutinib potentiated the anti-tumor effects of monotherapy with either agent by inducing a specific transcriptional cell-cycle arrest program that impairs DNA replication. The molecular actions of miR-28 and ibrutinib synergistically impair DNA replication by simultaneous inhibition of origin activation and fork progression. Moreover, we found that downregulation of the miR-28-plus-ibrutinib gene signature correlates with better survival of ABC-DLBCL patients. These results provide evidence for the effectiveness of a new miRNA-based ibrutinib combination therapy for DLBCL and unveil the miR-28-plus-ibrutinib gene signature as a new predictor of outcome in ABC-DLBCL patients.engVoRhttp://creativecommons.org/licenses/by/4.0/Lymphoma, Large B-Cell, DiffuseMicroRNAsHumansNeoplasm Recurrence, LocalAntineoplastic Combined Chemotherapy ProtocolsCombined Modality TherapyAtribución 4.0 Internacional37852959141068710.1038/s41419-023-06178-02041-4889Cell death & diseaseopen access