Differential Micro RNA Expression in PBMC from Multiple Sclerosis Patients |
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Authors: | David Otaegui Sergio E Baranzini Ruben Arma?anzas Borja Calvo Maider Mu?oz-Culla Puya Khankhanian I?aki Inza Jose A Lozano Tamara Castillo-Trivi?o Ana Asensio Javier Olaskoaga Adolfo López de Munain |
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Institution: | 1. Multiple Sclerosis Unit, Biodonostia Institute, San Sebastián, Spain.; 2. Neurology Department, University of California San Francisco, San Francisco, California, United States of America.; 3. Intelligent Systems Group, Computer Science Faculty, University of the Basque Country, San Sebastián, Spain.; 4. Neurology Department, Hospital Donostia, San Sebastián, Spain.;Max Planck Institute for Evolutionary Anthropology, Germany |
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Abstract: | Differences in gene expression patterns have been documented not only in Multiple Sclerosis patients versus healthy controls but also in the relapse of the disease. Recently a new gene expression modulator has been identified: the microRNA or miRNA. The aim of this work is to analyze the possible role of miRNAs in multiple sclerosis, focusing on the relapse stage. We have analyzed the expression patterns of 364 miRNAs in PBMC obtained from multiple sclerosis patients in relapse status, in remission status and healthy controls. The expression patterns of the miRNAs with significantly different expression were validated in an independent set of samples. In order to determine the effect of the miRNAs, the expression of some predicted target genes of these were studied by qPCR. Gene interaction networks were constructed in order to obtain a co-expression and multivariate view of the experimental data. The data analysis and later validation reveal that two miRNAs (hsa-miR-18b and hsa-miR-599) may be relevant at the time of relapse and that another miRNA (hsa-miR-96) may be involved in remission. The genes targeted by hsa-miR-96 are involved in immunological pathways as Interleukin signaling and in other pathways as wnt signaling. This work highlights the importance of miRNA expression in the molecular mechanisms implicated in the disease. Moreover, the proposed involvement of these small molecules in multiple sclerosis opens up a new therapeutic approach to explore and highlight some candidate biomarker targets in MS. |
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