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

Katherine A. Sanders, Miles C. Benton, Rod A. Lea, Vicki E. Maltby, Susan Agland, Nathan Griffin, Rodney J. Scott, Lotti Tajouri, Jeannette Lechner-Scott*

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number87
JournalClinical Epigenetics
Volume8
Issue number1
DOIs
Publication statusPublished - 27 Aug 2016

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    Sanders, K. A., Benton, M. C., Lea, R. A., Maltby, V. E., Agland, S., Griffin, N., Scott, R. J., Tajouri, L., & Lechner-Scott, J. (2016). Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells. Clinical Epigenetics, 8(1), [87]. https://doi.org/10.1186/s13148-016-0253-y