Résumé :
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The muscular disorders are a heterogeneous group of over thirty different inherited diseases characterized by muscle wasting and progressive weakness of variable distribution and severity, resulting in significant morbidity and disability. Although considerable progress has been made in our understanding of the overall complexity of the pathogenesis of the various muscular disorders, the underlying molecular pathways remain poorly understood. In light of their involvement in modulating cellular phenotypes we hypothesized that miRNAs might be involved in the regulation of the pathological pathways leading to muscle dysfunction. We describe a comprehensive miRNA expression profile aiming to identify new and modifying elements involved in the regulatory networks of muscle and the signature pattern of 185 miRNAs associated with ten common myopathological conditions in human. While five miRNAs (146b, 221, 155, 214, 222) were found to be consistently dysregulated in all samples analyzed in the study suggesting that these miRNAs are involved in a common underlying regulatory pathway among all diseases other miRNAs were identified to be dysregulated only in one given disease and not in any of the others thus pointing to their involvement in unique regulatory mechanism. The subsequent identification of potential target genes and the unraveling of biological signaling pathways involved in this regulatory level in these disorders, point to an additional dimension of regulation of muscle function mediated by miRNAs. Together with the tight post transcriptional regulation at the mRNA level identified in Duchenne and Miyoshi myopathy and specific mRNA:miRNA predicted interactions, some of which are directly involved in compensatory secondary response functions and others in muscle regeneration, these findings suggest an important role of miRNAs in the pathology of muscular dystrophy.
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