Comprehensive Analysis of lncRNA and miRNA Expression Profiles and ceRNA Network Construction in Osteoporosis

Abstract

Multiple profiling studies have identified a number of non-coding RNAs associated with the pathogenesis of human diseases. However, the exact regulatory mechanisms and functions of these non-coding RNAs in the development of osteoporosis have not yet been explored. Transcriptome gene expression and miRNA microarray data from peripheral blood monocytes of five high hip bone mineral density (BMD) subjects and five low hip BMD subjects were analyzed. Differentially expressed mRNAs, lncRNAs, and miRNAs were identified and subjected to functional enrichment analysis. Additionally, protein-protein interaction (PPI), lncRNA-mRNA, and mRNA-lncRNA-miRNA competing endogenous RNA (ceRNA) networks were constructed. Differential analysis revealed that 297 mRNAs, 151 lncRNAs, and 38 miRNAs were significantly differentially expressed between peripheral blood monocytes from high and low hip BMD subjects. Key genes including ACLY, HSPA5, and AKT1 were subsequently identified in the PPI network. Additionally, differentially expressed lncRNAs were primarily enriched in the citrate cycle (TCA cycle), biosynthesis of antibiotics, and carbon metabolism pathways. Finally, the mRNA-lncRNA-miRNA network revealed several key ceRNA regulatory relationships among the transcripts and non-coding RNAs. Key mRNAs and non-coding RNAs identified in the networks represent potential biomarkers or targets in the diagnosis and management of osteoporosis. Our findings represent a resource for further functional research on the ceRNA regulation mechanism of non-coding RNA in osteoporosis.

Keywords: Long non-coding RNAs; Osteoporosis; PPI; ceRNA network; miRNAs.