Identification of Potential miRNA-mRNA Regulatory Network in Denervated Muscular Atrophy by Bioinformatics Analysis

Background: Muscle atrophy caused by long-term denervation leads to the loss of skeletal muscle mass and strength, resulting in a poor recovery of functional muscles and decreasing quality of life. Increasing differentially expressed microRNAs (DEMs) have been reported to be involved in the pathogenesis of denervated muscle atrophy. However, there is still insufficient evidence to explain the role of miRNAs and their target genes in skeletal muscle atrophy. Therefore, an integrative exploration of the miRNA-mRNA regulatory network in denervated muscle atrophy is necessary. Methods: : Microarray GSE81914 was retrieved from the Gene Expression Omnibus (GEO) database, and the differentially expressed microRNAs (DEMs) were obtained by comparing the denervated muscle tissue with the innervated muscle. The miRNet database was used to predict the target genes of the obtained DEMs. Then Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by DAVID. The TF-miRNA and miRNA-mRNA regulatory networks were constructed using Cytoscape software. In addition, the key modules and hub genes were screened out from the protein-protein interaction (PPI) network and verified by qRT-PCR. Results: : A total of 21 (16 upregulated and 5 downregulated) DEMs were screened out in the GSE81914 dataset. Med1 was predicted and verified to be significantly upregulated, which may affect the process of denervated muscle atrophy by regulating mir-146b and mir-1949. 59 target genes were then predicted by submitting candidate DEMs to the miRNet database. GO and KEGG pathway enrichment analysis showed that target genes of DEMs were mainly enriched in the apoptotic process and PI3K/Akt signaling pathway. The key modules and hub genes were potentially modulated by mir-29b and mir-133a. Moreover, the qRT-PCR results confirmed the expression of COL1A1 and Ctgf are opposite to their related miRNAs. Conclusions: : In the study, a potential miRNA-mRNA regulatory network was firstly constructed in denervated muscle atrophy, in which the mir-29b-COL1A1 and mir-133a-Ctgf pathways may provide new insights into the pathogenesis and treatment.