Identification of a Potential MiRNA–mRNA Regulatory Network for Osteoporosis by Using Bioinformatics Methods: A Retrospective Study Based on the Gene Expression Omnibus Database
Lin Shi, Jianjun Wu, Baixing Chen, Shaoshuo Li, Hongxing Huang
Abstract
Introduction: As a systemic skeletal dysfunction, osteoporosis (OP) is characterized by low bone mass, impairment of bone microstructure, and a high global morbidity rate. There is increasing evidence that microRNAs (miRNAs) are associated with the pathogenesis of OP. Weighted gene co-expression network analysis (WGCNA) is a systematic method for identifying clinically relevant genes involved in disease pathogenesis. However, the study of the miRNA-messenger RNA (mRNA) regulatory network in combination with WGCNA in OP is still lacking. Methods: The GSE93883 and GSE7158 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs) and differentially expressed genes (DEGs) were analyzed with the limma package. OP-related miRNAs from the most clinically relevant module were identified by the WGCNA method. The overlap of DE-miRNAs and OP-related miRNAs was identified as OP-related DE-miRNAs. Both upstream transcription factors and downstream targets of OP-related DE-miRNAs were predicted by FunRich. An intersection of predicted target genes and DEGs was confirmed as downstream target genes of OP-related DE-miRNAs. With the use of clusterProfiler in R, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed on target genes. Finally, both the protein-protein interaction (PPI) network and miRNA-mRNA network were constructed and analyzed. Results: A total of 79 OP-related DE-miRNAs were obtained, most of which were predicted to be regulated by specificity protein 1 (SP1). Subsequently, 197 downstream target genes were screened out. The target genes were enriched in multiple pathways, including signaling pathways closely related to the onset of OP, such as Ras, PI3K-Akt, and ErbB signaling pathways. Through the construction of the OP-related miRNA-mRNA regulatory network, a hub network that may play a prominent role in the formation of OP was documented. Conclusion: By using WGCNA, we constructed a potential OP-related miRNA-mRNA regulatory network, offering a novel perspective on miRNA regulatory mechanisms in OP.