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ABC Efflux Transporters and the Circuitry of miRNAs

2020-04-23Artigo científico Acesso aberto
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dc.contributor.authorGomes, Bruno C.
dc.contributor.authorHonrado, Mónica
dc.contributor.authorArmada, Ana
dc.contributor.authorViveiros, Miguel
dc.contributor.authorRueff, José
dc.contributor.authorRueff, Jose
dc.contributor.authorRodrigues, António S.
dc.contributor.institutionCentre for Toxicogenomics and Human Health (ToxOmics)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.pblMDPI - Multidisciplinary Digital Publishing Institute
dc.date.accessioned2020-05-07T22:53:57Z
dc.date.available2020-05-07T22:53:57Z
dc.date.issued2020-04-23
dc.descriptionThis research was funded by Fundação de Ciência e Tecnologia (FCT), grant number UID-BIM-00009-2020 and GHTM-UID/Multi/04413/2013. The APC was funded by Fundação de Ciência e Tecnologia (FCT), grant number UID-BIM-00009-2020.
dc.description.abstractCancer drug resistance (CDR) is a major problem in therapeutic failure. Over 90% of patients with metastatic cancer present CDR. Several mechanisms underlie CDR, including the increased expression of efflux ABC transporters and epigenetic phenomena. Nevertheless, a topic that is not usually addressed is the mechanism underlying the loss of CDR once the challenge to these cells is withdrawn. A KCR cell line (doxorubicin-resistant, expressing ABCB1) was used to induce loss of resistance by withdrawing doxorubicin in culture medium. ABCB1 activity was analysed by fluorescence microscopy and flow cytometry through substrate (DiOC2) retention assays. The expression of 1008 microRNAs was assessed before and after doxorubicin withdrawal. After 16 weeks of doxorubicin withdrawal, a decrease of ABCB1 activity and expression occurred. Moreover, we determined a signature of 23 microRNAs, 13 underexpressed and 10 overexpressed, as a tool to assess loss of resistance. Through pathway enrichment analysis, “Pathways in cancer”, “Proteoglycans in cancer” and “ECM-receptor interaction” were identified as relevant in the loss of CDR. Taken together, the data reinforce the assumption that ABCB1 plays a major role in the kinetics of CDR, and their levels of expression are in the dependence of the circuitry of cell miRNAsen
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2317797
dc.identifier.doi10.3390/ijms21082985
dc.identifier.issn1422-0067
dc.identifier.otherPURE: 17890939
dc.identifier.otherPURE UUID: 861bf1a8-cbb1-45b6-b7cc-cdb1764c869e
dc.identifier.othercrossref: 10.3390/ijms21082985
dc.identifier.otherScopus: 85083843874
dc.identifier.otherPubMed: 32340269
dc.identifier.otherORCID: /0000-0001-9676-6251/work/73531623
dc.identifier.otherWOS: 000535565300327
dc.identifier.otherORCID: /0000-0001-5066-9982/work/177620833
dc.identifier.urihttp://hdl.handle.net/10362/97345
dc.identifier.urlhttps://www.mdpi.com/1422-0067/21/8/2985
dc.language.isoeng
dc.peerreviewedyes
dc.subjectcancer drug resistance
dc.subjectmicroRNAs
dc.subjectgene regulation
dc.subjectABC drug transporters
dc.subjectABCB1
dc.subjectMDR1
dc.subjectdoxorubicin
dc.subjectSDG 3 - Good Health and Well-being
dc.titleABC Efflux Transporters and the Circuitry of miRNAsen
dc.title.subtitleKinetics of Expression in Cancer Drug Resistanceen
dc.typejournal article
degois.publication.issue8
degois.publication.titleInternational Journal of Molecular Sciences
degois.publication.volume21
dspace.entity.typePublication
person.familyNameRueff
person.givenNameJose
person.identifier793666
person.identifier.ciencia-id0E15-908D-EA21
person.identifier.orcid0000-0002-8456-7295
person.identifier.ridE-6426-2013
person.identifier.scopus-author-id7006536439
rcaap.rightsopenAccess
relation.isAuthorOfPublication91a3b5ac-0328-498d-8cb8-08555b202306
relation.isAuthorOfPublication.latestForDiscovery91a3b5ac-0328-498d-8cb8-08555b202306

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