Irizar, H. 1, 2 , Muñoz-Culla, M. 1, 2 , Sáenz-Cuesta, M. 1, 2 , Osorio-Querejeta, I. 1, 2 , Prada, &. 2, 3 , Castillo-Triviño, T. 2, 3 , López de Munain, A. 1, 3, 4 , Olascoaga, J. 2, 3 & Otaegui, D. 1, 2
1 Biodonostia Research Institute
2 Spanish Multiple Sclerosis Net (REEM)
3 Hospital Universitario Donostia
4 Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED)
It has recently been revealed that small non-coding RNAs (sncRNAs), especially microRNAs (miRNAs), may play important roles in the pathogenesis of Multiple Sclerosis. miRNAs have been shown to be central players in the postrancriptional regulation of gene expression, whose study has incorporated a powerful mathematical tool: network modelling. With the aim of identifying the alterations at the sncRNA - mRNA regulatory level related to the disease, we have constructed sncRNA - mRNA coexpression networks. In total, 65 samples (22 patients in relapse and remission and 21 healthy controls) were collected for the study. RNA was isolated from peripheral blood leucocytes and whole genome gene expression was measured for both mRNAs (Human Gene 1.0 ST array (Affymetrix)) and sncRNAs (GeneChip miRNA array v1 (Affymetrix)). Our results highlight that sncRNA-mRNA coexpression networks, in contrast to most gene expression correlation networks, present a scale-free topology. They also reveal the central role of some miRNAs and snoRNAs in the global regulation of transcriptional activity. The analysis of differential connectivity performed on the status-specific networks (the relapse, remission and controls networks) shows that the three networks are very different (the number of common edges is very low). Finally, the network centrality measures of the disease-specific network identify some sncRNAs as having a central role in that network and that would be potential candidates for therapeutic targeting.