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)
Background: 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 whet...
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ir-10336-189452022-08-31T18:07:41Z 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) Pett, Robert D. McCarthy, Neil E. Le Dieu, Rifca Kerr, Jonathan R. Células mononucleares de sangre Células mononucleares de sangre Sangre periférica Anormalidades inmunológicas Células cancerígenas Identificación Exploración Activación Mecanismos PCR Enfermedades Síndrome de fatiga crónico Marcadores bioquímicos Blood mononuclear-cells Gene-expression profile Peripheral-blood Immunological abnormalities Cancer cells Identification PCR Exploration Activation Mechanisms Background: 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. 2016-03-16 2019-01-28T19:21:48Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 1932-6203 http://repository.urosario.edu.co/handle/10336/18945 https://doi.org/10.1371/journal.pone.0150904 eng info:eu-repo/semantics/openAccess application/pdf instname:Universidad del Rosario |
institution |
EdocUR - Universidad del Rosario |
collection |
DSpace |
language |
Inglés (English) |
topic |
Células mononucleares de sangre Células mononucleares de sangre Sangre periférica Anormalidades inmunológicas Células cancerígenas Identificación Exploración Activación Mecanismos PCR Enfermedades Síndrome de fatiga crónico Marcadores bioquímicos Blood mononuclear-cells Gene-expression profile Peripheral-blood Immunological abnormalities Cancer cells Identification PCR Exploration Activation Mechanisms |
spellingShingle |
Células mononucleares de sangre Células mononucleares de sangre Sangre periférica Anormalidades inmunológicas Células cancerígenas Identificación Exploración Activación Mecanismos PCR Enfermedades Síndrome de fatiga crónico Marcadores bioquímicos Blood mononuclear-cells Gene-expression profile Peripheral-blood Immunological abnormalities Cancer cells Identification PCR Exploration Activation Mechanisms Pett, Robert D. McCarthy, Neil E. Le Dieu, Rifca Kerr, Jonathan R. 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) |
description |
Background: 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. |
format |
Artículo (Article) |
author |
Pett, Robert D. McCarthy, Neil E. Le Dieu, Rifca Kerr, Jonathan R. |
author_facet |
Pett, Robert D. McCarthy, Neil E. Le Dieu, Rifca Kerr, Jonathan R. |
author_sort |
Pett, Robert D. |
title |
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) |
title_short |
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) |
title_full |
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) |
title_fullStr |
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) |
title_full_unstemmed |
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) |
title_sort |
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) |
publishDate |
2016 |
url |
http://repository.urosario.edu.co/handle/10336/18945 https://doi.org/10.1371/journal.pone.0150904 |
_version_ |
1743431122418663424 |
score |
12,131701 |