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MicroRNA expression profiling in patients with lamin A/C‐associated muscular dystrophy
Author(s) -
Sylvius Nicolas,
Bonne Gise'le,
Straatman Kees,
Reddy Thimma,
Gant Timothy W.,
Shackleton Sue
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-182915
Subject(s) - lmna , microrna , biology , wnt signaling pathway , lamin , muscular dystrophy , transcriptome , c2c12 , muscle disorder , genetics , gene , gene expression profiling , gene expression , myocyte , skeletal muscle , microbiology and biotechnology , bioinformatics , myogenesis , medicine , endocrinology
Mutations in the lamin A/C gene (LMNA) cause several disorders referred to as laminopathies, which include premature aging syndromes, lipodystrophy, and striated muscle disorders. There is evidence that lamin A/C plays a role in gene expression. MicroRNAs (miRNAs) are short noncoding RNAs regulating mRNAs involved in various biological processes, including the pathophysiology of striated muscles. Here, we profiled the expression of the miRNA transcriptome in skeletal muscle from patients with LMNA ‐related muscular dystrophy. Results show that control and patient groups can be distinguished based on their miRNA expression profile. Sixteen miRNAs are significantly dysregulated in patients compared with controls. Pathway enrichment analysis in the predicted targets of these miRNAs revealed pathways involved in muscle repair, such as MAPK, transforming growth factor‐β, and Wnt signaling. Interestingly, 9 of these miRNAs (hsa‐miR‐100, −127–3p, −148a, −136 ∗ , −192, −335, −376c, −489, and −502–3p) are highly expressed in fetal muscle, suggesting that the fetal miRNA gene program mediates a regenerative process. Overexpression of these miRNAs in C2C12 mouse myoblasts revealed that 3 of them (miR‐100, −192, and −335) participate in muscle proliferation and differentiation. We identified target genes that likely mediate this effect, which include the calcineurin gene PPP3CA. Our findings are the first to demonstrate that miRNA expression is affected in laminopathies.—Sylvius, N., Bonne, G., Straatman, K., Reddy, T., Gant, T. W., Shackleton, S. MicroRNA expression profiling in patients with lamin A/C‐associated muscular dystrophy. FASEB J. 25, 3966–3978 (2011). www.fasebj.org