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Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells

BACKGROUND: Immunoactivation is less evident in secondary progressive MS (SPMS) compared to relapsing-remitting disease. MicroRNA (miRNA) expression is integral to the regulation of gene expression; determining their impact on immune-related cell functions, especially CD4+ T cells, during disease pr...

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Autores principales: Sanders, Katherine A., Benton, Miles C., Lea, Rod A., Maltby, Vicki E., Agland, Susan, Griffin, Nathan, Scott, Rodney J., Tajouri, Lotti, Lechner-Scott, Jeannette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002332/
https://www.ncbi.nlm.nih.gov/pubmed/27570566
http://dx.doi.org/10.1186/s13148-016-0253-y
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author Sanders, Katherine A.
Benton, Miles C.
Lea, Rod A.
Maltby, Vicki E.
Agland, Susan
Griffin, Nathan
Scott, Rodney J.
Tajouri, Lotti
Lechner-Scott, Jeannette
author_facet Sanders, Katherine A.
Benton, Miles C.
Lea, Rod A.
Maltby, Vicki E.
Agland, Susan
Griffin, Nathan
Scott, Rodney J.
Tajouri, Lotti
Lechner-Scott, Jeannette
author_sort Sanders, Katherine A.
collection PubMed
description BACKGROUND: Immunoactivation is less evident in secondary progressive MS (SPMS) compared to relapsing-remitting disease. MicroRNA (miRNA) expression is integral to the regulation of gene expression; determining their impact on immune-related cell functions, especially CD4+ T cells, during disease progression will advance our understanding of MS pathophysiology. This study aimed to compare miRNA profiles of CD4+ T cells from SPMS patients to healthy controls (HC) using whole miRNA transcriptome next-generation sequencing (NGS). Total RNA was extracted from CD4+ T cells and miRNA expression patterns analyzed using Illumina-based small-RNA NGS in 12 SPMS and 12 HC samples. Results were validated in a further cohort of 12 SPMS and 10 HC by reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: The ten most dysregulated miRNAs identified by NGS were selected for qPCR confirmation; five (miR-21-5p, miR-26b-5p, miR-29b-3p, miR-142-3p, and miR-155-5p) were confirmed to be down-regulated in SPMS (p < 0.05). SOCS6 is targeted by eight of these ten miRNAs. Consistent with this, SOCS6 expression is up-regulated in SPMS CD4+ T cells (p < 0.05). This is of particular interest as SOCS6 has previously been shown to act as a negative regulator of T cell activation. CONCLUSIONS: Ninety-seven percent of miRNA candidates identified by NGS were down-regulated in SPMS. The down-regulation of miRNAs and increased expression of SOCS6 in SPMS CD4+ T cells may contribute to reduced immune system activity in progressive MS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0253-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-50023322016-08-29 Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells Sanders, Katherine A. Benton, Miles C. Lea, Rod A. Maltby, Vicki E. Agland, Susan Griffin, Nathan Scott, Rodney J. Tajouri, Lotti Lechner-Scott, Jeannette Clin Epigenetics Research BACKGROUND: Immunoactivation is less evident in secondary progressive MS (SPMS) compared to relapsing-remitting disease. MicroRNA (miRNA) expression is integral to the regulation of gene expression; determining their impact on immune-related cell functions, especially CD4+ T cells, during disease progression will advance our understanding of MS pathophysiology. This study aimed to compare miRNA profiles of CD4+ T cells from SPMS patients to healthy controls (HC) using whole miRNA transcriptome next-generation sequencing (NGS). Total RNA was extracted from CD4+ T cells and miRNA expression patterns analyzed using Illumina-based small-RNA NGS in 12 SPMS and 12 HC samples. Results were validated in a further cohort of 12 SPMS and 10 HC by reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: The ten most dysregulated miRNAs identified by NGS were selected for qPCR confirmation; five (miR-21-5p, miR-26b-5p, miR-29b-3p, miR-142-3p, and miR-155-5p) were confirmed to be down-regulated in SPMS (p < 0.05). SOCS6 is targeted by eight of these ten miRNAs. Consistent with this, SOCS6 expression is up-regulated in SPMS CD4+ T cells (p < 0.05). This is of particular interest as SOCS6 has previously been shown to act as a negative regulator of T cell activation. CONCLUSIONS: Ninety-seven percent of miRNA candidates identified by NGS were down-regulated in SPMS. The down-regulation of miRNAs and increased expression of SOCS6 in SPMS CD4+ T cells may contribute to reduced immune system activity in progressive MS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0253-y) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-27 /pmc/articles/PMC5002332/ /pubmed/27570566 http://dx.doi.org/10.1186/s13148-016-0253-y Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sanders, Katherine A.
Benton, Miles C.
Lea, Rod A.
Maltby, Vicki E.
Agland, Susan
Griffin, Nathan
Scott, Rodney J.
Tajouri, Lotti
Lechner-Scott, Jeannette
Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells
title Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells
title_full Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells
title_fullStr Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells
title_full_unstemmed Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells
title_short Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells
title_sort next-generation sequencing reveals broad down-regulation of micrornas in secondary progressive multiple sclerosis cd4+ t cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002332/
https://www.ncbi.nlm.nih.gov/pubmed/27570566
http://dx.doi.org/10.1186/s13148-016-0253-y
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