dc.contributor
Institut Català de la Salut
dc.contributor
[Reina-Ortiz C, Mozas MP, Anel A] Apoptosis, Immunity and Cancer Group, Department Biochemistry and Molecular and Cell Biology, Aragón Health Research Institute (IIS-Aragón), University of Zaragoza, Zaragoza, Spain. [Ovelleiro D] Unitat de Trastorns Neuromusculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Gao F] Institute of Regenerative Medicine and Biotherapy, University of Montpellier, INSERM, CNRS, University Hospital Center Montpellier, Montpellier, France. Immuno-Oncology Laboratory, School of Basic Medicine, Central South University, Changsha, China. [Villalba M] Institute of Regenerative Medicine and Biotherapy, University of Montpellier, INSERM, CNRS, University Hospital Center Montpellier, Montpellier, France
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Reina-Ortiz, Chantal
dc.contributor.author
Mozas Alonso, Pilar
dc.contributor.author
Ovelleiro Fraile, David
dc.contributor.author
Gao, Fei
dc.contributor.author
villalba, martin
dc.contributor.author
Anel, Alberto
dc.date.accessioned
2025-10-24T08:49:19Z
dc.date.available
2025-10-24T08:49:19Z
dc.date.issued
2023-09-19T09:20:55Z
dc.date.issued
2023-09-19T09:20:55Z
dc.date.issued
2023-08-31
dc.identifier
Reina-Ortiz C, Mozas MP, Ovelleiro D, Gao F, Villalba M, Anel A. Dynamic Changes in miRNA Expression during the Generation of Expanded and Activated NK Cells. Int J Mol Sci. 2023 Aug 31;24(17):13556.
dc.identifier
https://hdl.handle.net/11351/10305
dc.identifier
10.3390/ijms241713556
dc.identifier
001061159900001
dc.identifier.uri
http://hdl.handle.net/11351/10305
dc.description.abstract
Cytotoxicity; Immunotherapy; miRNA
dc.description.abstract
Citotoxicidad; Inmunoterapia; miARN
dc.description.abstract
Citotoxicitat; Immunoteràpia; miRNA
dc.description.abstract
Therapies based on allogenic Natural Killer (NK) cells are becoming increasingly relevant, and our laboratory has produced expanded and activated NK (eNK) cells that are highly cytotoxic against several hematological cancers when used alone or in combination with currently approved therapeutic monoclonal antibodies. In order to produce eNK cells, healthy human donor NK cells undergo a 20-day expansion protocol with IL-2, IL-15 and Epstein–Barr virus (EBV)-transformed lymphoblastoid feeder cells. In order to produce an even more potent eNK-based therapy, we must elucidate the changes our protocol produces within healthy NK cells. To understand the post-transcriptional changes responsible for the increased cytolytic abilities of eNK cells, we performed microRNA (miRNA) expression analysis on purified NK cells from day 0 and day 20 of the protocol using quantitative reverse transcription PCR (RT-qPCR). Of the 384 miRNAs profiled, we observed changes in the expression of 64 miRNAs, with especially significant changes in 7 of them. The up-regulated miRNAs of note were miRs-146a, -124, -34a, and -10a, which are key in the regulation of cell survival through the modulation of pro-apoptotic genes such as PUMA. The down-regulation of miRs-199a, -223, and -340 was also detected and is associated with the promotion of NK cell cytotoxicity. We validated our analysis using immunoblot and flow cytometry studies on specific downstream targets of both up- and down-regulated miRNAs such as PUMA and Granzyme B. These results corroborate the functional importance of the described miRNA expression patterns and show the wide variety of changes that occur in eNK cells at day 20.
dc.description.abstract
This research was supported by project PID2019-105128RB-I00 financed by MCIN/AEI/10.13039/501100011033/ and “FEDER Una manera de hacer Europa” and by Government of Aragon grant B31_20R.
dc.format
application/pdf
dc.format
application/pdf
dc.relation
International Journal of Molecular Sciences;24(17)
dc.relation
https://doi.org/10.3390/ijms241713556
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Teràpia cel·lular
dc.subject
ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Killer Cells, Natural
dc.subject
CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Cell- and Tissue-Based Therapy
dc.subject
ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::células asesinas naturales
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::tratamientos basados en células y tejidos
dc.title
Dynamic Changes in miRNA Expression during the Generation of Expanded and Activated NK Cells
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
