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

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.

Citation

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), Article 87. https://doi.org/10.1186/s13148-016-0253-y

• Journal Article Type: Article
• Acceptance Date: Aug 9, 2016
• Online Publication Date: Aug 27, 2016
• Publication Date: Aug 27, 2016
• Deposit Date: Aug 23, 2023
• Publicly Available Date: Sep 27, 2023
• Journal: Clinical Epigenetics
• Print ISSN: 1868-7075
• Electronic ISSN: 1868-7083
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 1
• Article Number: 87
• DOI: https://doi.org/10.1186/s13148-016-0253-y
• Keywords: Multiple sclerosis; Secondary progressive; MicroRNAs; Immunology; CD4+ T cells; Next-generation sequencing
• Public URL: https://hull-repository.worktribe.com/output/4366618
• Publisher URL: https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-016-0253-y