Transcriptomic landscape of cisplatin-resistant neuroblastoma cells

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dc.contributor.authorMerlos Rodrigo, Miguel Ángelcs
dc.contributor.authorBuchtelová, Hanacs
dc.contributor.authorJimenez Jimenez, Ana Mariacs
dc.contributor.authorAdam, Pavlínacs
dc.contributor.authorBabula, Petrcs
dc.contributor.authorHeger, Zbyněkcs
dc.contributor.authorAdam, Vojtěchcs
dc.coverage.issue3cs
dc.coverage.volume8cs
dc.date.accessioned2020-08-04T11:03:44Z
dc.date.available2020-08-04T11:03:44Z
dc.date.issued2019-03-31cs
dc.description.abstractThe efficiency of cisplatin (CDDP) is significantly hindered by the development of resistance during the treatment course. To gain a detailed understanding of the molecular mechanisms underlying the development of cisplatin resistance, we comparatively analyzed established a CDDP-resistant neuroblastoma cell line (UKF-NB-4(CDDP)) and its susceptible parental cells (UKF-NB-4). We verified increased chemoresistance of UKF-NB-4(CDDP) cells by analyzing the viability, induction of apoptosis and clonal efficiency. To shed more light on this phenomenon, we employed custom cDNA microarray (containing 2234 probes) to perform parallel transcriptomic profiling of RNA and identified that 139 genes were significantly up-regulated due to CDDP chemoresistance. The analyses of molecular pathways indicated that the top up-regulation scoring functions were response to stress, abiotic stimulus, regulation of metabolic process, apoptotic processes, regulation of cell proliferation, DNA repair or regulation of catalytic activity, which was also evidenced by analysis of molecular functions revealing up-regulation of genes encoding several proteins with a wide-spectrum of enzymatic activities. Functional analysis using lysosomotropic agents chloroquine and bafilomycin A1 validated their potential to re-sensitize UKF-NB-4(CDDP) cells to CDDP. Taken together, the identification of alterations in specific genes and pathways that contribute to CDDP chemoresistance may potentially lead to a renewed interest in the development of novel rational therapeutics and prognostic biomarkers for the management of CDDP-resistant neuroblastoma.en
dc.formattextcs
dc.format.extent1-19cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationCells. 2019, vol. 8, issue 3, p. 1-19.en
dc.identifier.doi10.3390/cells8030235cs
dc.identifier.issn2073-4409cs
dc.identifier.other156829cs
dc.identifier.urihttp://hdl.handle.net/11012/180502
dc.language.isoencs
dc.publisherMDPIcs
dc.relation"European Union (EU)" & "Horizon 2020"
dc.relation.ispartofCellscs
dc.relation.projectIdinfo:eu-repo/grantAgreement/EC/H2020/759585/EU//ToMeTuM
dc.relation.urihttp://www.mdpi.com/2073-4409/8/3/235cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/2073-4409/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectneuroblastomaen
dc.subjectcisplatinen
dc.subjectchemoresistanceen
dc.subjectmicroarrayen
dc.subjectlysosomesen
dc.subjecttransporten
dc.titleTranscriptomic landscape of cisplatin-resistant neuroblastoma cellsen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-156829en
sync.item.dbtypeVAVen
sync.item.insts2020.08.04 13:03:44en
sync.item.modts2020.08.04 12:20:14en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Chytré nanonástrojecs
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