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MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma

2025-04Artigo científico Acesso aberto
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dc.contributor.authorBergantim, Rui
dc.contributor.authorPeixoto da Silva, Sara
dc.contributor.authorPinto, Vanessa
dc.contributor.authorPereira, Joana M.
dc.contributor.authorSousa, Diana
dc.contributor.authorTrigo, Fernanda
dc.contributor.authorMatthiesen, Rune
dc.contributor.authorMatthiesen, Rune
dc.contributor.authorGuimarães, José E.
dc.contributor.authorVasconcelos, M. Helena
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutioniNOVA4Health - pólo NMS
dc.contributor.pblFrontiers Media
dc.date.accessioned2025-05-07T21:35:08Z
dc.date.available2025-05-07T21:35:08Z
dc.date.issued2025-04
dc.descriptionFunding Information: The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors acknowledge Sociedade Portuguesa de Hematologia/Associa\u00E7\u00E3o Portuguesa contra a Leucemia/AMGEN for funding this work (\u201CBOLSA DE INVESTIGA\u00C7\u00C3O 2017 EM MIELOMA M\u00DALTIPLO\u201D). Funding Information: The authors acknowledge the support of the i3S Bioinformatics Platform, the Flow Cytometry Laboratory of the Clinical Pathology Department, and the Hematology Laboratory of the Clinical Hematology Department of Centro Hospital S\u00E3o Jo\u00E3o, Porto, Portugal. SP is supported by FCT through PhD fellowship 2021.07467. BD. Publisher Copyright: Copyright © 2025 Bergantim, Peixoto da Silva, Pinto, Pereira, Sousa, Trigo, Matthiesen, Guimarães and Vasconcelos.
dc.description.abstractBackground: Multiple myeloma (MM) is a complex hematological malignancy with heterogeneous clinical and pathophysiological backgrounds that influence treatment responses and outcomes. Identifying biomarkers to predict drug response and guide treatment decisions, particularly regarding drug combinations, is essential to improve therapeutic efficacy and patient outcomes. This study explores the role of microRNAs (miRNAs/miRs) derived from bone marrow (BM) and peripheral blood (PB) in responses to treatment and survival outcomes in newly diagnosed MM (ndMM) patients. Methods: This study included twenty patients with ndMM undergoing first-line treatment with bortezomib, thalidomide, and dexamethasone. The miRNAs were isolated from BM and PB, and their profiles were analyzed using Next-Generation Sequencing (NGS), followed by validation of differentially expressed miRNAs by quantitative real-time PCR (qPCR). Clinical and response data were collected to assess correlations between miRNA levels, clinical characteristics, and patient outcomes. In silico analysis for target-prediction and gene ontology (GO) enrichment was performed to explore the potential biological and functional role of the identified miRNAs. Results: NGS profiling revealed several miRNAs differently expressed between treatment-refractory and sensitive patients, as well as between PB and BM. Among these, miR-665, miR-483-5p, miR-143-3p and miR-145-5p were selected for further validation by qPCR. It was observed that miR-665 was significantly elevated in treatment-refractory patients compared to treatment-sensitive patients. Additionally, miR-665 levels were higher in PB than in BM. Elevated miR-665 levels were associated with more aggressive disease characteristics and poorer clinical outcomes, including reduced overall survival. Discussion: Our preliminary findings suggest that miR-665 could potentially serve as a non-invasive tool for predicting drug resistance and guiding treatment decisions in MM. These findings also highlight the potential utility of miRNAs in liquid biopsies as a predictive tool of drug response in MM and could pave the way for personalized treatment strategies, improving patient outcomes. Future research is needed to validate these results in larger cohorts and explore the underlying mechanisms of miR-665 in MM pathogenesis and drug resistance.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2213642
dc.identifier.doi10.3389/fphar.2025.1465814
dc.identifier.issn1663-9812
dc.identifier.otherPURE: 115627998
dc.identifier.otherPURE UUID: 938efa16-728a-47f0-842a-16ca64bf4ac1
dc.identifier.otherScopus: 105003054037
dc.identifier.urihttp://hdl.handle.net/10362/182826
dc.identifier.urlhttps://www.scopus.com/pages/publications/105003054037
dc.language.isoeng
dc.peerreviewedyes
dc.subjectbiomarkers
dc.subjectdrug resistance
dc.subjectdrug response
dc.subjectmiRNAs
dc.subjectmultiple myeloma
dc.subjectPharmacology
dc.subjectPharmacology (medical)
dc.titleMicroRNA-665 and its potential role in drug response and survival outcomes in multiple myelomaen
dc.title.subtitlea preliminary studyen
dc.typejournal article
degois.publication.titleFrontiers in Pharmacology
degois.publication.volume16
dspace.entity.typePublication
person.familyNameMatthiesen
person.givenNameRune
person.identifier1319342
person.identifier.ciencia-idBB1A-A606-EE77
person.identifier.orcid0000-0002-6353-2616
person.identifier.scopus-author-id9741897800
rcaap.rightsopenAccess
relation.isAuthorOfPublication67181d3c-b83e-4151-9a74-0ea14aeb7f05
relation.isAuthorOfPublication.latestForDiscovery67181d3c-b83e-4151-9a74-0ea14aeb7f05

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