Identification and comparison of novel circular RNAs with associated co-expression and competing endogenous RNA networks in postmenopausal osteoporosis

J Orthop Surg Res. 2021 Jul 16;16(1):459. doi: 10.1186/s13018-021-02604-1.

Abstract

Background: Circular 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.

Methods: To 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.

Results: A 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.

Conclusion: The 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.

Keywords: Competitive endogenous RNA; Postmenopausal osteoporosis; Whole transcriptome sequencing; circRNAs.

MeSH terms

  • Computational Biology
  • Down-Regulation
  • Female
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • Osteoporosis, Postmenopausal / genetics*
  • Protein Interaction Maps
  • RNA, Circular / genetics*
  • RNA, Messenger / genetics*
  • Transcriptome
  • Up-Regulation

Substances

  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger