RT Journal Article
T1 miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication
A1 Fuertes, Teresa
A1 Álvarez Corrales, Emigdio
A1 Gómez Escolar, Carmen
A1 Ubieto Capella, Patricia
A1 Serrano Navarro, Álvaro
A1 De Molina, Antonio
A1 Méndez, Juan
A1 Ramiro, Almudena
A1 García-Yébenes Mena, Virginia Pilar
A1 García-Yébes Mena, Virginia Pilar
AB 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.
PB Springer Nature
SN 2041-4889
YR 2023
FD 2023¡
LK https://hdl.handle.net/20.500.14352/88881
UL https://hdl.handle.net/20.500.14352/88881
LA eng
NO Fuertes, T., Álvarez-Corrales, E., Gómez-Escolar, C. et al. miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication. Cell Death Dis 14, 687 (2023). https://doi.org/10.1038/s41419-023-06178-0
DS Docta Complutense
RD 10 abr 2025