Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/16761
Título
miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication.
Autor(es)
Fecha de publicación
2023-10-18
Cita
Cell Death Dis. 2023 Oct 18;14(10):687.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Lymphoma, Large B-Cell, Diffuse | MicroRNAs | Humans | Neoplasm Recurrence, Local | Antineoplastic Combined Chemotherapy Protocols | Combined Modality Therapy
Versión en línea
DOI
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