Comprehensive circRNA Analyses in Human Vertebrae of GIOP and Its Molecular Mechanism

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that play important roles in human diseases. However, the regulation of circRNAs in glucocorticoid-induced osteoporosis (GIOP) has not been reported. In this study, we performed high-throughput sequencing to identify altered circRNAs in the vertebrae from GIOP patients. A total of 65 clinical samples were collected in this study. Bioinformatics algorithms were employed to predict the target relationship between circRNAs and miRNAs and the circRNAs-miRNAs regulatory network. We focused on the top 10 significantly up-/downregulated circRNAs (hsa_circ_0004906, hsa_circ_0001172, hsa_circ_0005778, hsa_circ_0004276, hsa_circ_0005729, hsa_circ_0006173, hsa_circ_0007662, hsa_circ_0001451, hsa_circ_0001564, and hsa_circ_0108735) and measured their expression by qRT-PCR in clinical samples. Bioinformatics analyses demonstrated that 87 miRNAs were predicted in upregulated circRNAs and 104 miRNAs were predicted in downregulated circRNAs. The functional enrichment analysis showed these targeted miRNAs were significantly enriched in bone metabolism-related biological processes and pathways, including the MAPK signaling pathway, positive regulation of the metabolic process and metabolic pathways, etc. Collectively, our study revealed circRNA regulation and circRNAs-miRNAs regulatory network in GIOP for the first time, which provides a new perspective on the molecular mechanism of GIOP and lays a foundation for GIOP treatment.