Identifying hub genes and dysregulated pathways in Duchenne muscular dystrophy.

Purpose: The aim of this study was to identify the hub genes and dysregulated pathways in the progression of duchenne muscular dystrophy (DMD) and to unveil detailedly the cellular and molecular mechanisms associated with DMD for developing efficacious treatments in the future.

Material and methods: Three mRNA microarray datasets (GSE13608, GSE38417 and GSE109178) were downloaded from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) between DMD and normal tissues were obtained via R package. Function enrichment analyses were implemented respectively using DAVID online database. The network analysis of protein-protein interaction network (PPI) was conducted using String. Cytoscape and String were used to analyse modules and screen hub genes. The expression of the identified hub genes was confirmed in mdx mice through using qRT-PCR.

Results: 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 result of qRT-PCR suggested that 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.

Conclusion: 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.