Abstract
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.
Highlights
Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis induced by the long-term use of glucocorticoids (GCs) [1,2,3]
Six pairs of GIOP samples and control samples were used for highthroughput sequencing, while another thirty-one GIOP samples and twenty-two control samples were used for experimental validation. e diagnostic criteria for GIOP patients have characterized the long-term GC use and osteoporosis/osteopenia (T-score≤ −2.5/T-score > −2.5 and
Postmenopausal women, patients suffering from other diseases that may cause osteoporosis, and patients receiving any antiosteoporosis treatment were not included in this study. e inclusion criteria for the control group were as follows: (a) No metabolism diseases that might affect bone metabolism. (b) No osteoporosis and history of GC use. (c) Non-postmenopausal women. e clinical information was collected from all participants. e vertebral bone samples were collected by bone biopsy from two groups
Summary
Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis induced by the long-term use of glucocorticoids (GCs) [1,2,3]. Circular RNAs (circRNAs) represent a novel type of noncoding RNAs that are formed by the circularization of back-splicing events [6, 7]. CircRNAs are widely expressed in humans in a tissue- or cell-type-specific manner. Many studies have found that circRNAs could act as sponges of microRNAs (miRNAs) and competitively suppress miRNA activity to regulate gene expression [8, 9]. E association between human diseases and altered circRNA levels has been investigated. Accumulating evidence showed that circRNAs are potential diagnostic biomarkers for human diseases [10]. The global expression and potential mechanism of circRNAs in GIOP remain largely unknown
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