Sistema de Salut de Catalunya
Institut Català de la Salut
[Verdú-Bou M] Department of Medicine, Universitat Autònoma de Barcelona, Badalona, Spain. Lymphoid Neoplasms Group, Josep Carreras Leukaemia Research Institute, Badalona, Spain. [Baptista MJ] Lymphoid Neoplasms Group, Josep Carreras Leukaemia Research Institute, Badalona, Spain. [Ribeiro ML, Profitós-Pelejà N] Lymphoma Translational Group, Josep Carreras Leukaemia Research Institute, Badalona, Spain. [Méndez-López A] Department of Hematology, Institut Catala d’Oncologia–Germans Trias i Pujol University Hospital, Badalona, Spain. [Frontzek F] Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, Germany. Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada. [Abrisqueta P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Castellví J] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-07-08T07:51:30Z
2025-07-08T07:51:30Z
2025-06-24
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.
Article
Published version
English
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
Elsevier
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/
Articles científics - HVH [3440]
