Abstract

For the epigenetic characterization of neuromyelitis optica (NMO), we determined whether messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) are expressed differentially in subjects with and without NMO. lncRNA and mRNA expression profiles of NMO patients and healthy controls were generated by using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated by using gene ontology (GO) and pathway analyses. The microarray revealed that 1310 lncRNAs and 743 mRNAs differed in NMO patients from those in healthy controls. Pathway analysis then demonstrated that IL23-mediated signaling events, interferon gamma signaling, natural killer (NK)-κB signaling pathway, chemokine receptors that bind chemokines, GPCR ligand binding, and metabolic disorders of biological oxidation enzyme pathways play important roles in NMO. Several GO terms including cytokine stimulus, response to cytokine, immune response, cytokine-mediated signaling pathway, and response to chemical cytokine activity were enriched in gene lists, suggesting a potential correlation with NMO. Co-expression network analysis indicated that 183 lncRNAs and 458 mRNAs were included in the co-expression network. Our present study showed that these differentially expressed mRNAs and lncRNAs may play important roles in NMO and could provide basic information for new biomarkers or treatment targets to alleviate NMO.

Highlights

  • Neuromyelitis optica (NMO) is characterized by severe attacks of optic neuritis and/or longitudinally extensive transverse myelitis [1]

  • Results Long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) Profiles Differ in Patients with NMO and in Healthy Controls

  • 743 differentially expressed mRNAs reached the level of statistical significance in NMO patients compared to healthy controls

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Summary

Introduction

Neuromyelitis optica (NMO) is characterized by severe attacks of optic neuritis and/or longitudinally extensive transverse myelitis [1]. A significant proportion of NMO patients are seropositive for antibodies that target aquaporin-4 [2], the main water channel in the central nervous system (CNS), and localize to astrocyte processes [3]. The epigenetic characteristics of this disease are not completely understood. Long noncoding RNAs (lncRNAs) are typified by a length of transcription longer than 200 nucleotides that is not translated into proteins [4]. Increasing scientific interest in these factors stems from previous investigations showing that lncRNAs exert their regulatory effects on gene expression levels, involving epigenetic regulation, transcriptional regulation, and posttranscriptional regulation in the form of RNA [5]. Emerging evidence suggests the decisive participation of lncRNAs in such autoimmune diseases as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), and multiple sclerosis (MS) [7]

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