Identifying hub genes and dysregulated pathways in duchenne muscular dystrophy.

Although progress had been made in clarifying the pathogenesis of Duchenne muscular dystrophy (DMD), significant work needs to be done to unveil detailedly the cellular and molecular mechanisms associated with DMD for developing efficacious treatments. To identify the hub genes and dysregulated pathways in the progression of DMD, GSE13608, GSE38417 and GSE109178 mRNA microarray datasets were downloaded from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) between DMD and normal tissues were obtained, and function enrichment analyses were carried out. The network analysis of protein-protein interaction network (PPI) was conducted. STRING and Cytoscape were used to analyse modules and screen hub genes. In total, 519 DEGs were identified, consisting of 393 upregulated genes and 126 downregulated genes. The enriched functions and pathways of the DEGs mainly involve extracellular matrix organization, collagen fibril organization, interferon-gamma-mediated signaling pathway, muscle contraction, endoplasmic reticulum lumen, MHC class II receptor activity, phagosome, graft-versus-host disease, cardiomyocytes, calcium signaling pathway. Twelve hub genes were discovered and biological process analysis proved that these genes were mainly enriched cell cycle, cell division. The expression of the identified hub genes was confirmed in mdx mice through using qRT-PCR. Increase in expression of CD44, ECT2, TYMS, MAGEL2, HLA-DMA, SERPINH1, TNNT2 was confirmed in mdx mice and the downregulation of ASB2 and LEPREL1 was also observed. In conclusion, DEGs and hub genes identified in the current research help us probe the molecular mechanisms underlying the pathogenesis and progression of DMD, and provide candidate targets for diagnosis and treatment of DMD.