Identification of hub genes, miRNAs and regulatory factors relevant for Duchenne muscular dystrophy by bioinformatics analysis

Abstract

Purpose

Duchenne muscular dystrophy (DMD) is currently the most commonly diagnosed form of muscular dystrophy due to mutations in the dystrophin gene. However, its pathological process remains unknown and there is a lack of specific molecular biomarkers. The aim of our study is to explore key regulatory connections underlying the progression of DMD.

Materials and methods

The gene expression profile dataset GSE38417 of DMD was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between DMD patients and healthy controls were screened using geo2R, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. Then a protein–protein interaction (PPI) network and sub-network of modules were constructed. To investigate the regulatory network underlying DMD, a global triple network including miRNAs, mRNAs and transcription factors (TFs) was constructed.

Results

A total of 1811 DEGs were found between the DMD and control groups, among which HERC5, SKP2 and FBXW5 were defined as hub genes with a degree of connectivity >35 in the PPI network. Furthermore, the five TFs ZNF362, ATAT1, SPI1, TCF12 and ABCF2, as well as the eight miRNAs miR-124a, miR-200b/200c/429, miR-19a/b, miR-23a/b, miR-182, miR-144, miR-498 and miR-18a/b were identified as playing crucial roles in the molecular pathogenesis of DMD.

Conclusions

This paper provides a comprehensive perspective on the miRNA–TF–mRNA co-regulatory network underlying DMD, although the bioinformatic findings need further validation in future studies.

Keywords:

• Duchenne muscular dystrophy
• bioinformatics analysis
• differentially expressed genes

Availability of data and materials

The dataset generated and/or analyzed during the current study are available from the Gene Expression Omnibus repository GSE38417.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [No. 81760328].