2026-06-14T03:38:22Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/167612024-09-27T08:08:14Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Fuertes, Teresa author Álvarez-Corrales, Emigdio author Gómez-Escolar, Carmen author Ubieto-Capella, Patricia author Serrano-Navarro, Álvaro author de Molina, Antonio author Méndez, Juan author Ramiro, Almudena R author de Yébenes, Virginia G author 2023-10-18 Diffuse 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. Cell Death Dis. 2023 Oct 18;14(10):687. 10.1038/s41419-023-06178-0 2041-4889 Cell death & disease 37852959 http://hdl.handle.net/20.500.12105/16761 miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication.