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Distinctive patterns of microRNA expression in primary muscular disorders.

Abstract
The primary muscle disorders are a diverse group of diseases caused by various defective structural proteins, abnormal signaling molecules, enzymes and proteins involved in posttranslational modifications, and other mechanisms. Although there is increasing clarification of the primary aberrant cellular processes responsible for these conditions, the decisive factors involved in the secondary pathogenic cascades are still mainly obscure. Given the emerging roles of microRNAs (miRNAs) in modulation of cellular phenotypes, we searched for miRNAs regulated during the degenerative process of muscle to gain insight into the specific regulation of genes that are disrupted in pathological muscle conditions. We describe 185 miRNAs that are up- or down-regulated in 10 major muscular disorders in humans [Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophies types 2A and 2B, Miyoshi myopathy, nemaline myopathy, polymyositis, dermatomyositis, and inclusion body myositis]. Although five miRNAs were found to be consistently regulated in almost all samples analyzed, pointing to possible involvement of a common regulatory mechanism, others were dysregulated only in one disease and not at all in the other disorders. Functional correlation between the predicted targets of these miRNAs and mRNA expression demonstrated tight posttranscriptional regulation at the mRNA level in DMD and Miyoshi myopathy. Together with direct mRNA-miRNA predicted interactions demonstrated in DMD, some of which are involved in known secondary response functions and others that are involved in muscle regeneration, these findings suggest an important role of miRNAs in specific physiological pathways underlying the disease pathology.
AuthorsIris Eisenberg, Alal Eran, Ichizo Nishino, Maurizio Moggio, Costanza Lamperti, Anthony A Amato, Hart G Lidov, Peter B Kang, Kathryn N North, Stella Mitrani-Rosenbaum, Kevin M Flanigan, Lori A Neely, Duncan Whitney, Alan H Beggs, Isaac S Kohane, Louis M Kunkel
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 104 Issue 43 Pg. 17016-21 (Oct 23 2007) ISSN: 0027-8424 [Print] United States
PMID17942673 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • MicroRNAs
  • RNA, Messenger
Topics
  • Cluster Analysis
  • Gene Expression Regulation
  • Humans
  • MicroRNAs (genetics)
  • Muscular Dystrophies (genetics, pathology)
  • Oligonucleotide Array Sequence Analysis
  • Principal Component Analysis
  • RNA, Messenger (genetics, metabolism)
  • Reproducibility of Results
  • Signal Transduction

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