- Title
- Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+T cells
- Creator
- Sanders, Katherine A.; Benton, Miles C.; Lea, Rod A.; Maltby, Vicki E.; Agland, Susan; Griffin, Nathan; Scott, Rodney J.; Tajouri, Lotto; Lechner-Scott, Jeannette
- Relation
- Clinical Epigenetics Vol. 8
- Publisher Link
- http://dx.doi.org/10.1186/s13148-016-0253-y
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2016
- 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.
- Subject
- multiple sclerosis; secondary progressive; microRNAs; immunology; CD4+ T cells; next-generation sequencing
- Identifier
- http://hdl.handle.net/1959.13/1327989
- Identifier
- uon:25795
- Identifier
- ISSN:1868-7083
- Rights
- © 2016 The Author(s). Open Access This 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.
- Language
- eng
- Full Text
- Reviewed
- Hits: 8230
- Visitors: 9013
- Downloads: 466
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 711 KB | Adobe Acrobat PDF | View Details Download |