Logo do repositório
 
Publicação

Functional effects of differentially expressed microRNAs in A549 cells exposed to MWCNT-7 or crocidolite

2020-08-01Artigo científico Acesso restrito
Ver registo simples
dc.contributor.authorVentura, Célia
dc.contributor.authorVieira, Luís
dc.contributor.authorSilva, Catarina
dc.contributor.authorSousa-Uva, António
dc.contributor.authorSilva, Maria João
dc.date.accessioned2021-03-08T15:45:08Z
dc.date.available2021-03-08T15:45:08Z
dc.date.issued2020-08-01
dc.description.abstractMulti-walled carbon nanotubes (MWCNT) are engineered nanomaterials widely used in industrial and biomedical applications. Yet, MWCNT inhalation may induce pulmonary adverse effects, and the MWCNT-7 (Mitsui-7) has been classified as possibly carcinogenic to humans. However, its molecular mechanisms of action are poorly understood and there are no biomarkers of exposure for occupational monitoring. Several pulmonary diseases, including lung cancer, have been associated with alterations in microRNA expression that are used as biomarkers of disease progression, and differentially-expressed microRNAs (DE miRNAs) can also allow understanding the molecular effects induced by a toxicant. In this study, we identify DE miRNAs in A549 alveolar epithelial cells following 24 h exposure to MWCNT-7 or crocidolite, as well as their enriched cellular functional pathways. These indicate that both materials change cell survival, differentiation and proliferative properties under the influence of AMPK, FoxO, TGF-β and Hippo pathways, and their metabolic activity and cell-to-cell communication. In addition, MWCNT-7 affects the actin cytoskeleton, ubiquitin mediated proteolysis, and ECM-receptor interactions; crocidolite the PI3K-Akt and mTOR pathways, endocytosis, and central carbon metabolism. Since deregulation of these pathways may be related to carcinogenesis, an interaction network of DE miRNAs and corresponding target cancer-related genes was constructed, highlighting the carcinogenic potential of Mitsui-7.pt_PT
dc.description.abstractHighlights: Multi-walled carbon nanotubes (MWCNT) are nanomaterials widely used that may induce pulmonary adverse effects upon inhalation; A profile of differentially expressed (DE) miRNAs in A549 alveolar cells was identified following exposure to MWCNT-7 and crocidolite using NGS; Both materials change AMPK, FoxO, TGF-β and Hippo pathways, the cell metabolic activity and cell-to-cell communication; MWCNT-7 affects the actin cytoskeleton, ubiquitin mediated proteolysis, and ECM-receptor interactions; Crocidolite affects the PI3K-Akt and mTOR pathways, endocytosis, and central carbon metabolism; An interaction network of DE miRNAs and corresponding target cancer-related genes highlighted the carcinogenic potential of MWCNT-7, even at low dose and short-term exposure.pt_PT
dc.description.sponsorshipThis work was funded by FCT/MCTES, Project ToxApp4NanoCELFI (PTDC/SAU-PUB/32587/2017) through national funds (PIDDAC) and ToxOmics (UID/BIM/00009/2013). It is also a result of the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by FCT.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationToxicol Lett. 2020 Aug 1;328:7-18. doi: 10.1016/j.toxlet.2020.04.002. Epub 2020 Apr 18.pt_PT
dc.identifier.doi10.1016/j.toxlet.2020.04.002pt_PT
dc.identifier.issn0378-4274
dc.identifier.urihttp://hdl.handle.net/10400.18/7362
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/ EUROTOXpt_PT
dc.relationA predictive toxicology approach to characterize potential respiratory effects of functionalized nanocellulose fibres in a co-culture system
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S0378427420301120?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectA549 Cellspt_PT
dc.subjectAsbestos, Crocidolitept_PT
dc.subjectCarbonpt_PT
dc.subjectCell Survivalpt_PT
dc.subjectGene Expressionpt_PT
dc.subjectHumanspt_PT
dc.subjectMicroRNAs Expressionpt_PT
dc.subjectNanotubes, Carbonpt_PT
dc.subjectProto-Oncogene Proteins c-aktpt_PT
dc.subjectPulmonary Alveolipt_PT
dc.subjectMitsui-7pt_PT
dc.subjectmicroRNA-target Gene Networkpt_PT
dc.subjectCarcinogenesispt_PT
dc.subjectPathway Analysispt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleFunctional effects of differentially expressed microRNAs in A549 cells exposed to MWCNT-7 or crocidolitept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleA predictive toxicology approach to characterize potential respiratory effects of functionalized nanocellulose fibres in a co-culture system
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-PUB%2F32587%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F00009%2F2013/PT
oaire.citation.endPage18pt_PT
oaire.citation.startPage7pt_PT
oaire.citation.titleToxicology Letterspt_PT
oaire.citation.volume328pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876
person.familyNameVentura
person.familyNameSilva
person.givenNameCélia
person.givenNameMaria Joao
person.identifier2056460
person.identifier.ciencia-id6116-89BA-C617
person.identifier.ciencia-id7710-643D-97A3
person.identifier.orcid0000-0002-0637-2222
person.identifier.orcid0000-0002-6060-0716
person.identifier.scopus-author-id55944437600
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationfa89f42b-12a4-47bd-a4fb-0f65cbc06885
relation.isAuthorOfPublicationa7763685-7c34-468d-b958-9dd0aca66db4
relation.isAuthorOfPublication.latestForDiscoveryfa89f42b-12a4-47bd-a4fb-0f65cbc06885
relation.isProjectOfPublication0c494598-bc88-4e48-8032-cb9f4b4c0b0f
relation.isProjectOfPublicatione9cc9728-4f09-4e3a-b30d-53d4429986fb
relation.isProjectOfPublication.latestForDiscoverye9cc9728-4f09-4e3a-b30d-53d4429986fb

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
ventura2020_miRNAs.pdf
Tamanho:
2.75 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

DGH - Artigos em revistas internacionais