Advances in MicroRNAs in Pathophysiology of Duchenne Muscular Dystrophy.

Abstract

Duchenne muscular dystrophy (DMD) is a severe, progressive muscle disorder caused by pathogenic variants in the DMD gene, which encodes dystrophin, a protein essential for maintaining muscle integrity. Reduced or absent dystrophin expression results in sarcolemmal instability, chronic inflammation, oxidative stress, impaired muscle regeneration, and fibrosis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally and significantly influence multiple pathological processes in DMD. Specific miRNAs, including miR-146a, miR-155, miR-378, and miR-711, modulate inflammation primarily through the NF-κB signaling pathway. Others, such as miR-21, miR-31, miR-128, miR-144, and miR-379, regulate oxidative stress responses via the NRF2 antioxidant pathway. Muscle-specific miRNAs (myomiRs), notably miR-1, miR-133a/b, miR-206, miR-486, and miR-499, are critical for muscle regeneration, and their dysregulation impairs satellite cell function and muscle repair. Additionally, miRNAs such as miR-21, miR-29a/c, and miR-199a-5p play significant roles in fibrosis development. The dysregulation of these miRNAs contributes to the complex pathophysiology of DMD, underscoring their potential as biomarkers for disease progression and therapeutic response. Understanding the specific roles of these miRNAs provides valuable insights into the molecular mechanisms underlying DMD and may facilitate the identification of novel therapeutic targets.