Abstract

The aim of this research was to discover microRNAs and circular RNAs with varying expression in osteoporosis patients who have been given denosumab and to explore the correlation between microRNAs, messenger RNAs and circular RNAs and the drugs. As a first finding, we found differential microRNA and circular RNA expression in patients treated with denosumab for osteoporosis. Our next step was to identify microRNAregulated genes and genes that correspond to circular RNAs and then to perform enrichment analysis on those genes. We explored the correlation between circular RNA, microRNA and messenger RNA for the drugs as a concluding step. Our findings revealed 18 microRNA and 239 circular RNAs that were increased, and 15 microRNAs and 316 circular RNAs that were reduced in osteoporosis patients treated with denosumab in comparison to those who had not been treated. Analysis of Kyoto encyclopedia of genes and genomes pathway revealed that pathways targeted by differentially expressed microRNAs were notably enriched and they are axon guidance, proteoglycans in cancer, sphingolipid signalling and erythroblastic oncogene B signalling. The gene ontology enrichment analysis, meanwhile, revealed that pathways targeted by differentially expressed microRNAs were notably enriched and they are wingless-related integration site-induced cell-cell signalling, glutamatergic synapse and deoxyribonucleic acid-binding transcription activator activity. Analysis of Kyoto encyclopedia of genes and genomes pathway revealed that pathways significantly enriched by differentially expressed circular RNA were Salmonella infection, endocytosis, Fc gamma R-mediated phagocytosis and spinocerebellar ataxia; conversely, gene ontology enrichment analysis indicated that pathways significantly enriched by differentially expressed circular RNA were positive regulation of cellular catabolic process and cadherin binding. Considered to be the most important microRNAs involved the hsa-miR-424-5p, hsa-miR-1299, hsa-miR-195-5, hsa-miR-320d and hsa-miR-548am-3p are in the functions of denosumab in osteoporosis. A number of critical circular RNAs have been identified, such as hsa_circ_0005044, hsa_ circ_0005027, hsa_circ_0005657, hsa_circ_0005988 and hsa_circ_0013386.