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.