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oai:recercat.cat:11351/133682025-10-24T10:44:54Zcom_2072_378070com_2072_378040col_2072_378092

2025-10-24T10:44:54Z urn:hdl:11351/13368 The role of miR-150-5p/E2F3/survivin axis in the pathogenesis of plasmablastic lymphoma and its therapeutic potential Verdú-Bou, Miriam Baptista, Maria Joao Ribeiro, Marcelo Lima Profitós-Pelejà, Núria Frontzek, Fabian Méndez, Aleix Abrisqueta, Pau Castellvi, Josep Cèl·lules B - Tumors - Aspectes genètics Limfomes - Aspectes genètics MicroARN DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse::Plasmablastic Lymphoma Other subheadings::Other subheadings::Other subheadings::/genetics DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::Inhibitor of Apoptosis Proteins::Survivin CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso::linfoma plasmablástico Otros calificadores::Otros calificadores::Otros calificadores::/genética ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos y proteínas de señalización intracelular::proteínas reguladoras de la apoptosis::proteínas inhibidoras de la apoptosis::survivina COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN Pathogenesis; Plasmablastic lymphoma Patogènesi; Limfoma plasmablàstic Patogénesis; Linfoma plasmablástico 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. This study was supported by a grant from Instituto de Salud Carlos III, Ministerio de Economia y Competitividad (PI19/01588) and by the Josep Carreras Foundation, Spain. 2025-10-24T10:44:54Z 2025-10-24T10:44:54Z 2025-07-08T07:51:30Z 2025-07-08T07:51:30Z 2025-06-24 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/13368 Blood Advances;9(12) https://doi.org/10.1182/bloodadvances.2025016180 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Elsevier Scientia