Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head

Osteonecrosis of the femoral head (ONFH) accounts for as many as 18% of total hip arthroplasties. Knowledge of genetic changes and molecular abnormalities could help identify individuals considered to be at a higher risk of developing ONFH. In this study, we sought to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) associated with ONFH by integrated bioinformatics analyses as well as to construct the miRNA-mRNA regulatory network involving in the pathogenesis of ONFH. We performed differential expression analysis using a gene expression profile GSE123568 and a miRNA expression profile GSE89587 deposited in the Gene Expression Omnibus and identified 47 DEmiRs (24 upregulated miRNAs and 23 downregulated miRNAs) and 529 DEGs (218 upregulated genes and 311 downregulated genes). Gene Ontology enrichment analyses of DEGs suggested that DEGs were significantly enriched in neutrophil activation, cytosol, and ubiquitin-protein transferase activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs revealed that DEGs were significantly enriched in transcriptional misregulation in cancer. DEGs-based miRNA-mRNA regulatory networks were obtained by searching miRNA-mRNA prediction databases, TargetScan, miTarBase, miRMap, miRDB, and miRanda databases. Then, overlapped miRNAs were selected between these putative miRNAs and DEmiRs between ONFH and non-ONFH, and pairs of the DEmiR-DEG regulatory network were finally depicted. There were 12 nodes and 64 interactions for upDEmiR-downDEG regulatory networks and 6 nodes and 16 interactions for downDEmiR-upDEG regulatory networks. Using the STRING database, we established a protein-protein interaction network based on the overlapped DEGs between ONFH and non-ONFH. C5AR1, CDC27, CDC34, KAT2B, CPPED1, TFDP1, and MX2 were identified as the hub genes. The present study characterizes the miRNA profile, gene profile, and miRNA-mRNA regulatory network in ONFH, which may contribute to the interpretation of the pathogenesis of ONFH and the identification of novel biomarkers and therapeutic targets for ONFH.