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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.creatorPetty, Robert D.spa
dc.creatorMcCarthy, Neil E.spa
dc.creatorLe Dieu, Rifcaspa
dc.creatorKerr, Jonathan R.spa
dc.date.accessioned2020-06-11T13:21:45Z
dc.date.available2020-06-11T13:21:45Z
dc.date.created2016spa
dc.description.abstractBackgroundChronic 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.MethodsmiRNA 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.ResultsMicroarray 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 hsa-miR-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.ConclusionThis 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.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0150904
dc.identifier.issn1932-6203
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24892
dc.language.isoeng
dc.publisherPublic Library of Sciencespa
dc.relation.citationIssueNo. 3
dc.relation.citationTitlePLOS ONE
dc.relation.citationVolumeVol. 11
dc.relation.ispartofPLOS ONE, ISSN:1932-6203, Vol.11, No.3 (2016); pp. -spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subjectcélulas mononucleares de sangrespa
dc.subjectperfil de expresión génicaspa
dc.subjectSangre periféricaspa
dc.subjectanormalidades inmunológicasspa
dc.subjectCélulas cancerígenasspa
dc.subjectidentificaciónspa
dc.subjectpcrspa
dc.subjectexploraciónspa
dc.subjectactivaciónspa
dc.subjectmecanismosspa
dc.subject.keywordblood mononuclear-cellsspa
dc.subject.keywordgene-expression profilespa
dc.subject.keywordperipheral-bloodspa
dc.subject.keywordimmunological abnormalitiesspa
dc.subject.keywordcancer cellsspa
dc.subject.keywordidentificationspa
dc.subject.keywordpcrspa
dc.subject.keywordexplorationspa
dc.subject.keywordactivationspa
dc.subject.keywordmechanismsspa
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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