The role of miR-150-5p/E2F3/survivin axis in the pathogenesis of plasmablastic lymphoma and its therapeutic potential

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.

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Publication Details

Journal
Blood Advances
Published
2025-04-09
DOI
https://doi.org/10.1182/bloodadvances.2025016180
Citations
3
Primary Topic
Viral-associated cancers and disorders
Type
article
Field-Weighted Citation Impact
3.14

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article

The role of miR-150-5p/E2F3/survivin axis in the pathogenesis of plasmablastic lymphoma and its therapeutic potential

Núria Profitós-Pelejà, Pau Abrisqueta, Miriam Verdú-Bou, Manel Esteller et al.
3 citations
Blood Advances
Viral-associated cancers and disorders
3.14
article

The role of miR-150-5p/E2F3/survivin axis in the pathogenesis of plasmablastic lymphoma and its therapeutic potential

Núria Profitós-Pelejà, Pau Abrisqueta, Miriam Verdú-Bou, Manel Esteller, Antonio Salar, Fina Climent, Annette M. Staiger, Mariana Bastos‐Oreiro, José Luís Mate, Javier Menárguez, Gaël Roué, Georg Lenz, Marcelo Lima Ribeiro, Miguel Alcoceba, Eva M. González-Barca, José‐Tomás Navarro, Aleix Méndez López, Fabian Frontzek, German Ott, Gustavo Tapia, Juan‐Manuel Sancho, Josep Castellví, Ioannis Anagnostopoulos, Maria João Baptista, M. Pellicer
article en
3 citations

Abstract

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.

Blood AdvancesVol. 9(12)
Hebron University (PS), Universitat Autònoma de Barcelona (ES), University of Würzburg (DE), Spinal Cord Injury BC (CA), Bellvitge University Hospital (ES), Robert Bosch Hospital (DE), Hospital General Universitario Gregorio Marañón (ES), Institut d'Investigació Biomédica de Bellvitge (ES), Josep Carreras Leukaemia Research Institute (ES), University Hospital Münster (DE), Institut Català d'Oncologia (ES), Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology (DE), Vall d'Hebron Hospital Universitari (ES), Hospital Del Mar (ES), Instituto de Investigación Biomédica de Salamanca (ES), Badalona Serveis Assistencials (ES), Centro de Investigación del Cáncer (ES), Duran i Reynals Hospital (ES), Hospital Municipal de Badalona (ES), Hospital Universitari Germans Trias i Pujol (ES), Centro de Investigación Biomédica en Red de Cáncer (ES)
Instituto de Salud Carlos III, Institut de Recerca contra la Leucèmia Josep Carreras
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Openalex Percentile: Top 8%
Viral-associated cancers and disorders
3.14
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