Dlk1-Dio3 cluster miRNAs regulate mitochondrial functions in the dystrophic muscle in Duchenne muscular dystrophy

• DOI: 10.26508/lsa.202201506
• Publication Date: 2022-10-20T19:45:12Z
• Authors: Ai Vu Hong; Nathalie Bourg; Peggy Sanatine; Jerome Poupiot; Karine Charton; Evelyne Gicquel; Emmanuelle Massou...; Marco Spinazzi; Isabelle Richard; David Israeli
• Keywords: mdx mouse

Duchenne muscular dystrophy (DMD) is a severe muscle disease caused by impaired expression of dystrophin. Whereas mitochondrial dysfunction thought to play an important role in DMD, the mechanism this remains be clarified. Here we demonstrate that DMD and other dystrophies, large number Dlk1-Dio3 clustered miRNAs (DD-miRNAs) are coordinately up-regulated regenerating myofibers serum. To characterize biological effect dysregulation, 14 DD-miRNAs were simultaneously overexpressed vivo mouse muscle. Transcriptomic analysis revealed highly similar changes between ectopically overexpressing mdx diaphragm, with naturally DD-miRNAs. Among commonly dysregulated pathway found repressed metabolism, oxidative phosphorylation (OxPhos) particular. Knocking down iPS-derived skeletal myotubes resulted increased OxPhos activities. The data suggest (1) mediators dystrophic muscle, (2) metabolism particular targeted These findings provide insight into dystrophy.