Abstract
BackgroundCircular RNAs (circRNAs) are emerging as crucial regulators in various human diseases. So far, the expression profile and regulatory mechanism of circRNAs in postmenopausal osteoporosis (PMOP) are less studied and should be deciphered urgently. Herein, we aimed to reveal key circRNAs affecting PMOP and clarify their compounding regulatory actions.MethodsTo reveal key circRNAs affecting PMOP and clarify their compounding regulatory actions, whole transcriptome sequencing and bioinformatics analysis were performed to identify differentially expressed circRNAs (DECs). The expression pattern and regulatory networks of DECs in peripheral blood mononuclear cells (PBMCs) were unearthed.ResultsA total of 373 DECs comprising 123 intronic, 100 antisense, 70 exonic, 55 intergenic, and 25 sense-overlapping circRNAs were identified. Among these, 73 circRNAs were upregulated and 300 were downregulated. These DECs exerted pivotal functions in the pathogenesis of PMOP as demonstrated by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The circRNA-miRNA-mRNA co-expression network comprising 28 DECs, 145 miRNAs, and 175 differentially expressed mRNAs predicted the possible mechanism of the pathogenesis and progression of PMOP.ConclusionThe results of the present study provided a further comprehension of circRNA-associated competing endogenous RNA regulatory mechanism in PMOP. The steadily expressed and disease-specific DECs may serve as promising diagnostic and prognostic biomarkers for PMOP.
Highlights
Osteoporosis, a pervasive public health concern worldwide, manifests as the depletion of bone mineral with structure deterioration of bone tissue and results in a predisposition to fragility fractures, especially in women [1]
To alleviate the public health burden of postmenopausal osteoporosis (PMOP), it is a prerequisite to screen out the population at high risk for fracture, which entails the identification of more rapid, specific, and sensitive bone turnover markers (BTMs) [3]
Three paired fresh venous blood samples were collected for whole transcriptome sequencing and 30 paired samples were used for quantitative evaluation using realtime quantitative polymerase chain reaction
Summary
Osteoporosis, a pervasive public health concern worldwide, manifests as the depletion of bone mineral with structure deterioration of bone tissue and results in a predisposition to fragility fractures, especially in women [1]. CircRNAs are expressed more steadily and abundantly than the standard linear transcription of homologous genes due to the closedloop structure, which prevents degradation by RNA exonuclease [8]. In this way, disease-specific and tissue-specific circRNAs could act as biomarkers for the early diagnosis and prediction of certain diseases theoretically [10]. The present study aimed to uncover accurate circRNA biomarkers and provide clues for exploring the underlying mechanism of PMOP. The expression profile and regulatory mechanism of circRNAs in postmenopausal osteoporosis (PMOP) are less studied and should be deciphered urgently. We aimed to reveal key circRNAs affecting PMOP and clarify their compounding regulatory actions
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