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

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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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Chronic Progressive Multiple Sclerosis
MicroRNAs
Down-Regulation
T-Lymphocytes
RNA
Gene Expression Regulation
Transcriptome
Reverse Transcription
Disease Progression
Immune System
Polymerase Chain Reaction

Cite this

Sanders, K. A., Benton, M. C., Lea, R. A., Maltby, V. E., Agland, S., Griffin, N., ... 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
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. In: Clinical Epigenetics. 2016 ; Vol. 8, No. 1.
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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.",
author = "Sanders, {Katherine A.} and Benton, {Miles C.} and Lea, {Rod A.} and Maltby, {Vicki E.} and Susan Agland and Nathan Griffin and Scott, {Rodney J.} and Lotti Tajouri and Jeannette Lechner-Scott",
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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.

In: Clinical Epigenetics, Vol. 8, No. 1, 87, 27.08.2016.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells

AU - Sanders, Katherine A.

AU - Benton, Miles C.

AU - Lea, Rod A.

AU - Maltby, Vicki E.

AU - Agland, Susan

AU - Griffin, Nathan

AU - Scott, Rodney J.

AU - Tajouri, Lotti

AU - Lechner-Scott, Jeannette

PY - 2016/8/27

Y1 - 2016/8/27

N2 - 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.

AB - 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.

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U2 - 10.1186/s13148-016-0253-y

DO - 10.1186/s13148-016-0253-y

M3 - Article

VL - 8

JO - Clinical Epigenetics

JF - Clinical Epigenetics

SN - 1868-7075

IS - 1

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