000127777 001__ 127777
000127777 005__ 20241125101144.0
000127777 0247_ $$2doi$$a10.3390/ijms241713556
000127777 0248_ $$2sideral$$a134914
000127777 037__ $$aART-2023-134914
000127777 041__ $$aeng
000127777 100__ $$0(orcid)0000-0003-2683-0814$$aReina-Ortiz, Chantal
000127777 245__ $$aDynamic Changes in miRNA Expression during the Generation of Expanded and Activated NK Cells
000127777 260__ $$c2023
000127777 5060_ $$aAccess copy available to the general public$$fUnrestricted
000127777 5203_ $$aTherapies based on allogenic Natural Killer (NK) cells are becoming increasingly relevant, and our laboratory has produced expanded and activated NK (eNK) cells that are highly cytotoxic against several hematological cancers when used alone or in combination with currently approved therapeutic monoclonal antibodies. In order to produce eNK cells, healthy human donor NK cells undergo a 20-day expansion protocol with IL-2, IL-15 and Epstein–Barr virus (EBV)-transformed lymphoblastoid feeder cells. In order to produce an even more potent eNK-based therapy, we must elucidate the changes our protocol produces within healthy NK cells. To understand the post-transcriptional changes responsible for the increased cytolytic abilities of eNK cells, we performed microRNA (miRNA) expression analysis on purified NK cells from day 0 and day 20 of the protocol using quantitative reverse transcription PCR (RT-qPCR). Of the 384 miRNAs profiled, we observed changes in the expression of 64 miRNAs, with especially significant changes in 7 of them. The up-regulated miRNAs of note were miRs-146a, -124, -34a, and -10a, which are key in the regulation of cell survival through the modulation of pro-apoptotic genes such as PUMA. The down-regulation of miRs-199a, -223, and -340 was also detected and is associated with the promotion of NK cell cytotoxicity. We validated our analysis using immunoblot and flow cytometry studies on specific downstream targets of both up- and down-regulated miRNAs such as PUMA and Granzyme B. These results corroborate the functional importance of the described miRNA expression patterns and show the wide variety of changes that occur in eNK cells at day 20.
000127777 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B31-20R$$9info:eu-repo/grantAgreement/ES/FEDER/Una manera de hacer Europa$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00
000127777 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000127777 590__ $$a4.9$$b2023
000127777 592__ $$a1.179$$b2023
000127777 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b66 / 313 = 0.211$$c2023$$dQ1$$eT1
000127777 593__ $$aMedicine (miscellaneous)$$c2023$$dQ1
000127777 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b68 / 231 = 0.294$$c2023$$dQ2$$eT1
000127777 593__ $$aPhysical and Theoretical Chemistry$$c2023$$dQ1
000127777 593__ $$aComputer Science Applications$$c2023$$dQ1
000127777 593__ $$aInorganic Chemistry$$c2023$$dQ1
000127777 593__ $$aSpectroscopy$$c2023$$dQ1
000127777 593__ $$aOrganic Chemistry$$c2023$$dQ1
000127777 593__ $$aMolecular Biology$$c2023$$dQ2
000127777 593__ $$aCatalysis$$c2023$$dQ2
000127777 594__ $$a8.1$$b2023
000127777 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000127777 700__ $$0(orcid)0000-0001-5956-4319$$aMozas, Mª Pilar$$uUniversidad de Zaragoza
000127777 700__ $$aOvelleiro, David
000127777 700__ $$aGao, Fei
000127777 700__ $$aVillalba, Martín
000127777 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, Alberto$$uUniversidad de Zaragoza
000127777 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000127777 773__ $$g24, 17 (2023), 13556 [17 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000127777 8564_ $$s5981778$$uhttps://zaguan.unizar.es/record/127777/files/texto_completo.pdf$$yVersión publicada
000127777 8564_ $$s2603993$$uhttps://zaguan.unizar.es/record/127777/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000127777 909CO $$ooai:zaguan.unizar.es:127777$$particulos$$pdriver
000127777 951__ $$a2024-11-22-12:03:36
000127777 980__ $$aARTICLE