The role of miR-150-5p/E2F3/survivin axis in the pathogenesis of plasmablastic lymphoma and its therapeutic potential
Verdú-Bou, Miriam (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Baptista, Maria Joao (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ribeiro, ML (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Méndez-López, Aleix (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Profitós-Pelejà, Núria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Frontzek, Fabian (University Hospital of Münster (Alemanya))
Roué, Gaël (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Mate, José Luís (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pellicer, Mireia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Abrisqueta, Pau (Hospital Universitari Vall d'Hebron)
Castellvi, Josep (Hospital Universitari Vall d'Hebron)
Bastos, Mariana (Hospital General Universitario Gregorio Marañón)
Menárguez, Javier (Hospital General Universitario Gregorio Marañón)
Alcoceba, Miguel (Hospital Universitario de Salamanca)
González Barca, Eva (Institut Català d'Oncologia)
Climent, Fina (Institut d'Investigació Biomèdica de Bellvitge)
Salar Silvestre, Antonio (Hospital del Mar (Barcelona, Catalunya))
Sancho, Juan-Manuel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Staiger, Annette M. (Robert Bosch Hospital (Stuttgart, Alemanya))
Ott, German (Robert Bosch Hospital (Stuttgart, Alemanya))
Anagnostopoulos, Ioannis (Julius-Maximilians-Universität Würzburg)
Esteller, M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Lenz, Georg (University Hospital of Münster (Alemanya))
Tapia, Gustavo (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Navarro Ferrando, José Tomás (Universitat Autònoma de Barcelona. Departament de Medicina)

Data:	2025
Resum:	Plasmablastic lymphoma (PBL) is an uncommon and aggressive B-cell lymphoma with a poor prognosis. Some studies have described genetic alterations in PBL, but its transcriptome has been scarcely studied, and molecular mechanisms driving lymphomagenesis remain poorly understood. Our goal was to delineate transcriptomic profiles to identify potential biomarkers for novel targeted therapy in PBL. RNA sequencing uncovered an enrichment of cell cycle-related genes, including MYC and E2F targets, and genes involved in G2/M checkpoint in PBL. Microarray analyses discovered 2 microRNA expression signatures depending on the presence of MYC translocation. Interestingly, miR-150-5p was downregulated, whereas E2F3 and BIRC5 (survivin), a cell cycle activator and an antiapoptotic regulator, respectively, were upregulated. Increasing miR-150-5p in PBL-1 cells induced G1 cell cycle arrest, suppressed proliferation by transcriptionally repressing E2F3, and promoted apoptosis by the downregulation of BIRC5. Interestingly, the miR-150-5p tumor suppressor activity was diminished in E2F3 -knockdown cells. The combined inhibition of E2F3 and survivin attenuated lymphomagenesis in PBL cells and suppressed tumor growth in a chorioallantoic membrane-derived xenograft model of PBL. Overall, our study highlights the pivotal role of the miR-150-5p/E2F3/survivin axis in boosting PBL lymphomagenesis and unveils new therapeutic targets for this lymphoma.
Ajuts:	Instituto de Salud Carlos III PI19/01588
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Blood advances, Vol. 9 Núm. 12 (June 2025) , p. 2953-2967, ISSN 2473-9537

DOI: 10.1182/bloodadvances.2025016180
PMID: 40203244

15 p, 4.1 MB

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