Expression Profile of Long Noncoding RNAs in Peripheral Blood Mononuclear Cells from Multiple Sclerosis Patients

Abstract

SummaryAimsLong noncoding RNAs (lncRNAs) play a key role in regulating immunological functions. Their impact on the chronic inflammatory disease multiple sclerosis (MS), however, remains unknown. We investigated the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) of patients with MS and attempt to explain their possible role in the process of MS.MethodsFor this study, we recruited 26 patients with MS according to the revised McDonald criteria. Then, we randomly chose 6 patients for microarray analysis. Microarray assays identified outstanding differences in lncRNA expression, which were verified through real‐time PCR. LncRNA functions were annotated for target genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and regulatory relationships between lncRNAs and target genes were analyzed using the “cis” and “trans” model.ResultsThere were 2353 upregulated lncRNAs, 389 downregulated lncRNAs, 1037 upregulated mRNAs, and 279 downregulated mRNAs in patients with MS compared to healthy control subjects (fold change >2.0). Real‐time PCR results of six aberrant lncRNAs were consistent with the microarray data. The coexpression network comprised 864 lncRNAs and 628 mRNAs. Among differentially expressed lncRNAs, 10 lncRNAs were predicted to have 10 cis‐regulated target genes, and 33 lncRNAs might regulate their trans target genes.ConclusionsWe identified a subset of dysregulated lncRNAs and mRNAs. The differentially expressed lncRNAs may be important in the process of MS. However, the specific molecular mechanisms and biological functions of these lncRNAs in the pathogenesis of MS need further study.

Linc‐MAF‐4 regulates T h 1/T h 2 differentiation and is associated with the pathogenesis of multiple sclerosis by targeting MAF

“…There is growing interest in the contribution of non‐coding RNAs to gene regulation in patients with MS (19). New medications could be developed to modulate the expression of specific noncoding RNAs and subsequent gene activity that is involved in proliferation and activation of effector cells.…”

“…Long intergenic noncoding RNAs (lncRNAs) are composed of .200 nucleotides that regulate gene expression at the post-transcriptional level (13,14). Many biologic processes, such as development, homeostasis, pathophysiologic changes, and immune responses are regulated by lncRNAs (15)(16)(17)(18)(19). Numerous lncRNAs are cell specific.…”

Long noncoding RNAs in autoimmune diseases

“…86 Fang Zhang et al identified a subset of dysregulated lncRNAs in the peripheral blood mononuclear cells (PBMCs) of MS patients using an RNA microarray method. 87,88 Their data prove that differentially expressed lncRNAs might be important in the process of MS. Infection with murine encephalomyelitis virus (TMEV) is an important method for establishing MS mouse models.…”

“…lnc‐MAF‐4, as a Th1‐specific lncRNA, is involved in the pathogenesis of MS, specifically via regulation of encephalitogenic T cells . Fang Zhang et al identified a subset of dysregulated lncRNAs in the peripheral blood mononuclear cells (PBMCs) of MS patients using an RNA microarray method . Their data prove that differentially expressed lncRNAs might be important in the process of MS.…”

HOTAIR but not ANRIL long non‐coding RNA contributes to the pathogenesis of multiple sclerosis

“…VDR is a nuclear receptor that heterodimerizes with the retinoid X receptor, which after ligation with 1,25(OH) 2 D recognizes vitamin D response elements (VDREs) within regulatory regions of targeted genes . Importantly, several studies have revealed that VD can impact the expression of lncRNAs and that peripheral blood mononuclear cells (PBMCs) and serum of patients with MS exhibit altered levels of lncRNAs compared with controls . Studies aiming to understand the mechanisms underpinning lncRNA regulation of gene expression have greatly benefited from the discovery of HOX transcript antisense intergenic RNA (HOTAIR), a lncRNA molecule encoded within the HoxC gene cluster on chromosome 12 and transcribed in an antisense manner with respect to the canonical HoxC genes .…”