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MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c : Potential diagnostic biomarkers in natural killer (NK) cells of patients with Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME)

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dc.creatorPett, Robert D.
dc.creatorMcCarthy, Neil E.
dc.creatorLe Dieu, Rifca
dc.creatorKerr, Jonathan R.
dc.creator.googlePett, Robert D.spa
dc.creator.googleMcCarthy, Neil E.spa
dc.creator.googleLe Dieu, Rifcaspa
dc.creator.googleKerr, Jonathan R.spa
dc.date.accessioned2019-01-28T19:21:48Z
dc.date.available2019-01-28T19:21:48Z
dc.date.created2016-03-16
dc.date.issued2016
dc.description.abstractBackground: Chronic Fatigue Syndrome (CFS/ME) is a complex multisystem disease of unknown aetiology which causes debilitating symptoms in up to 1% of the global population. Although a large cohort of genes have been shown to exhibit altered expression in CFS/ME patients, it is currently unknown whether microRNA (miRNA) molecules which regulate gene translation contribute to disease pathogenesis. We hypothesized that changes in microRNA expression in patient leukocytes contribute to CFS/ME pathology, and may therefore represent useful diagnostic biomarkers that can be detected in the peripheral blood of CFS/ME patients. Methods: miRNA expression in peripheral blood mononuclear cells (PBMC) from CFS/ME patients and healthy controls was analysed using the Ambion Bioarray V1. miRNA demonstrating differential expression were validated by qRT-PCR and then replicated in fractionated blood leukocyte subsets from an independent patient cohort. The CFS/ME associated miRNA identified by these experiments were then transfected into primary NK cells and gene expression analyses conducted to identify their gene targets. Results: Microarray analysis identified differential expression of 34 miRNA, all of which were up-regulated. Four of the 34 miRNA had confirmed expression changes by qRT-PCR. Fractionating PBMC samples by cell type from an independent patient cohort identified changes in miRNA expression in NK-cells, B-cells and monocytes with the most significant abnormalities occurring in NK cells. Transfecting primary NK cells with hsa-miR-99b or hsamiR-330-3p, resulted in gene expression changes consistent with NK cell activation but diminished cytotoxicity, suggesting that defective NK cell function contributes to CFS/ME pathology. Conclusion: This study demonstrates altered microRNA expression in the peripheral blood mononuclear cells of CFS/ME patients, which are potential diagnostic biomarkers. The greatest degree of miRNA deregulation was identified in NK cells with targets consistent with cellular activation and altered effector function. © 2016 Petty et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0150904
dc.identifier.issn1932-6203
dc.identifier.urihttp://repository.urosario.edu.co/handle/10336/18945
dc.language.isoengspa
dc.relation.citationEndPage19
dc.relation.citationIssueNo. 3
dc.relation.citationStartPage1
dc.relation.citationTitlePLoS ONE
dc.relation.citationVolumeVol. 11
dc.relation.ispartofPLoS ONE, ISSN: 1932-6203, Vol. 11/No. 3 (2016); pp.1-19spa
dc.relation.urihttps://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0150904&type=printablespa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.rights.cchttps://creativecommons.org/licenses/by/4.0/spa
dc.source.bibliographicCitation(2002) A Report of the CFS/ME Working Group.spa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subjectCélulas mononucleares de sangrespa
dc.subjectCélulas mononucleares de sangrespa
dc.subjectSangre periféricaspa
dc.subjectAnormalidades inmunológicasspa
dc.subjectCélulas cancerígenasspa
dc.subjectIdentificaciónspa
dc.subjectExploraciónspa
dc.subjectActivaciónspa
dc.subjectMecanismosspa
dc.subjectPCRspa
dc.subject.ddcEnfermedadesspa
dc.subject.keywordBlood mononuclear-cellseng
dc.subject.keywordGene-expression profileeng
dc.subject.keywordPeripheral-bloodeng
dc.subject.keywordImmunological abnormalitieseng
dc.subject.keywordCancer cellseng
dc.subject.keywordIdentificationeng
dc.subject.keywordPCReng
dc.subject.keywordExplorationeng
dc.subject.keywordActivationeng
dc.subject.keywordMechanismseng
dc.subject.lembSíndrome de fatiga crónicospa
dc.subject.lembMarcadores bioquímicosspa
dc.titleMicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c : Potential diagnostic biomarkers in natural killer (NK) cells of patients with Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME)spa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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