Abstract
BackgroundSeveral studies have revealed a potential role for both small nucleolar RNAs (snoRNAs) and microRNAs (miRNAs) in the physiopathology of relapsing-remitting multiple sclerosis (RRMS). This potential implication has been mainly described through differential expression studies. However, it has been suggested that, in order to extract additional information from large-scale expression experiments, differential expression studies must be complemented with differential network studies. Thus, the present work is aimed at the identification of potential therapeutic ncRNA targets for RRMS through differential network analysis of ncRNA – mRNA coexpression networks. ncRNA – mRNA coexpression networks have been constructed from both selected ncRNA (specifically miRNAs, snoRNAs and sdRNAs) and mRNA large-scale expression data obtained from 22 patients in relapse, the same 22 patients in remission and 22 healthy controls. Condition-specific (relapse, remission and healthy) networks have been built and compared to identify the parts of the system most affected by perturbation and aid the identification of potential therapeutic targets among the ncRNAs.ResultsAll the coexpression networks we built present a scale-free topology and many snoRNAs are shown to have a prominent role in their architecture. The differential network analysis (relapse vs. remission vs. controls’ networks) has revealed that, although both network topology and the majority of the genes are maintained, few ncRNA – mRNA links appear in more than one network. We have selected as potential therapeutic targets the ncRNAs that appear in the disease-specific network and were found to be differentially expressed in a previous study.ConclusionsOur results suggest that the diseased state of RRMS has a strong impact on the ncRNA – mRNA network of peripheral blood leukocytes, as a massive rewiring of the network happens between conditions. Our findings also indicate that the role snoRNAs have in targeted gene silencing is a widespread phenomenon. Finally, among the potential therapeutic target ncRNAs, SNORA40 seems to be the most promising candidate.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1396-5) contains supplementary material, which is available to authorized users.
Highlights
Several studies have revealed a potential role for both small nucleolar RNAs and microRNAs in the physiopathology of relapsing-remitting multiple sclerosis (RRMS)
Taking into account the length of the vectors used for computing correlations (i.e. number of samples (N) = 65), the matrix obtained in the correlation analysis was cut at Pearson’s R < −0.42 (p = 0.0005) and all the mRNA – mRNA and ncRNA – ncRNA correlations were removed
With the aim of studying the coexpression relations between selected ncRNAs and mRNAs and the effect that the diseased-state of multiple sclerosis exerts on those relations, ncRNA – mRNA negative correlation networks have been built from both whole genome mRNA and ncRNA expression data obtained from MS patients in relapse and remission and healthy controls
Summary
Several studies have revealed a potential role for both small nucleolar RNAs (snoRNAs) and microRNAs (miRNAs) in the physiopathology of relapsing-remitting multiple sclerosis (RRMS). This potential implication has been mainly described through differential expression studies. Alterations in miRNAs have been related to multiple sclerosis (MS), as in the last years several works have studied miRNA expression in a variety of tissues (peripheral blood, brain and CSF) from MS patients and in the Experimental Autoimmune Encephalitis (EAE) animal model (reviewed in [10]) All these studies found alterations in miRNA expression levels in MS patients compared to healthy controls and an implication for miRNAs seems to be evident. Little overlap is observed among different studies, probably due to the difference in the miRNA profiling technology, the complexity of the tissue being studied and the relatively small sample size of all studies
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