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

Liwei Yu,Zhoulei Jiang,Tong Xu,Tengfei Yao

doi:10.1155/2021/8076598

Abstract

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.

Highlights

Osteonecrosis of the femoral head (ONFH), known as avascular necrosis or aseptic necrosis, is a common but complex disease related to ischemia of the femoral head, which destroys the structural integrity of the femoral head [1]
With log2 |fold change (FC)| ≥ 1 and an adjusted p value less than 0.05 as the cutoff value, a total of 47 differentially expressed miRNAs (DEmiRs) consisting of 24 upregulated miRNAs and 23 downregulated miRNAs between ONFH patients and healing patients were
From the enrichment results of the biological process (BP) category, we found that differential expressed genes (DEGs) were significantly enriched in neutrophil activation (GO: 0042119), neutrophil degranulation (GO: 0043312), vesiclemediated transport (GO: 0016192), neutrophil activation involved in immune response (GO: 0002283), and neutrophilmediated immunity (GO: 0002446)

Summary

Introduction

Osteonecrosis of the femoral head (ONFH), known as avascular necrosis or aseptic necrosis, is a common but complex disease related to ischemia of the femoral head, which destroys the structural integrity of the femoral head [1]. ONFH refers to death of bone cells caused by the damage of microvascular circulation [2]. The occurrence of ONFH in the general population have rarely been reported on epidemiological studies in China, a nationally representative survey estimated that 8.12 million people aged 15 years and over in China were associated with ONFH during 2012-2013 [3]. More evidence have manifested that young adults and middle-aged people, especially male, are prone to suffer from ONFH [4]. Tons of studies have been performed on the etiology, epidemiology, diagnosis, and treatment of ONFH, the exact origin still remains unclear. Some studies have indicated that the trauma [5] and nontraumatic factors involving corticosteroid use [6], habitual drinking [7], and cigarette smoking [8] were strongly contributed to the prevalence of ONFH

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Results

Conclusion