Identification of Hub Genes and Dysregulated Pathways in Duchenne Muscular Dystrophy (DMD)

Abstract

Purpose

This study aims to identify hub genes and dysregulated pathways in the progression of Duchenne muscular dystrophy (DMD) and elucidate the cellular and molecular mechanisms associated with DMD to develop effective treatments.

Materials and Methods

• Datasets: Three mRNA microarray datasets (GSE13608, GSE38417, and GSE109178) were downloaded from the Gene Expression Omnibus (GEO).
• Analysis Tools: The R package was used to identify differentially expressed genes (DEGs) between DMD and normal tissues. Functional enrichment analyses were performed using the DAVID online database.
• Network Analysis: The STRING database and Cytoscape were used to analyze protein-protein interaction (PPI) networks and identify hub genes.
• Validation: Expression of hub genes was validated in mdx mice using qRT-PCR.

Results

• Differentially Expressed Genes (DEGs): 519 DEGs were identified, including 393 upregulated genes and 126 downregulated genes.
• Enriched Functions and Pathways: The identified DEGs were involved in:
  • Extracellular matrix organization
  • Collagen fibril organization
  • Interferon-gamma-mediated signaling pathway
  • Muscle contraction
  • Calcium signaling pathway
• Hub Genes: Twelve hub genes were discovered, with biological process analysis indicating enrichment in cell cycle and cell division.
• qRT-PCR Validation:
  • Increased expression: CD44, ECT2, TYMS, MAGEL2, HLA-DMA, SERPINH1, TNNT2
  • Decreased expression: ASB2, LEPREL1

Conclusion

The identification of DEGs and hub genes in this study advances our understanding of the molecular mechanisms underlying the pathogenesis and progression of DMD. These findings provide potential targets for diagnosis and treatment of DMD.