Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches

Osteoporosis is a degenerative osteoarthropathy commonly found in old people and postmenopausal women. Many studies showed that microRNAs (miRNAs) can regulate the expression of osteoporosis-related genes and are abnormally expressed in patients with osteoporosis. miRNAs therefore have the potential to serve as biomarkers of osteoporosis. In this study, the limma package was used for the differential expression analysis of mRNA expression profiles and 357 significantly differentially expressed genes (DEGs) were obtained. Metascape was used for functional enrichment analysis of DEGs. The result revealed that DEGs were mainly enriched in signaling pathways like MAPK6/MAPK4. Based on the STRING database, the protein-protein interaction (PPI) network of DEGs was constructed. MCODE was used to analyze the functional subsets, and a key functional subset composed of 9 genes was screened out. In addition, the miRNA-mRNA regulatory interaction network (RegIN) was analyzed by the CyTargetLinker plugin, which generated 55 miRNA-mRNA regulatory interactions. Through literature searching, the osteoporosis-related gene FOXO1 in the key functional subset was determined to be the main object of the study. In qRT-PCR assay, the expression of the predicted miRNAs was tested in peripheral blood mononuclear cells of mice with osteoporosis, in which 13 miRNAs were remarkably highly expressed. All in all, this study, based on bioinformatics analysis and testing assay of miRNA expression, determined the potential biomarkers of osteoporosis.