Construction of a Potentially Functional circRNA-miRNA-mRNA Network in Intervertebral Disc Degeneration by Bioinformatics Analysis

Biomed Res Int. 2021 Aug 4:2021:8352683. doi: 10.1155/2021/8352683. eCollection 2021.

Abstract

Background: The competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms are known to play a pivotal role in intervertebral disc degeneration (IDD). Our research intended to establish a ceRNA regulatory network related to IDD through bioinformatics analyses.

Methods: The expression profiles of circRNA, miRNA, and mRNA were obtained from the public Gene Expression Omnibus (GEO) datasets. Then, we use sequence-based bioinformatics methods to select differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs), or circRNAs (DEcircRNAs) related to IDD. We used ChEA3 to verify the targets of transcription factors (TFs). Then, we used DAVID to annotate the DEmRNAs. Finally, we constructed a potentially circRNA-miRNA-mRNA network related to IDD by predicting in the database (ENCORI, TargetScan, miRecords, miRmap, and circBank).

Results: We identified 31 common DEmRNAs by Venn analysis, of which MMP2 was regarded as the key hub genes. Simultaneously, miR-423-5p and miR-185-5p were predicted as the upstream molecules of MMP2. Furthermore, a total of six DEcircRNAs were predicted as the upstream circRNAs of miR-423-5p and miR-185-5p. Then, a potential circRNA-miRNA-mRNA network related to IDD was constructed by bioinformatics analysis.

Conclusion: A comprehensive ceRNA regulatory network was constructed, which was found to be significant in IDD progression.

MeSH terms

  • Computational Biology / methods*
  • Disease Progression
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • Intervertebral Disc Degeneration / genetics*
  • Matrix Metalloproteinase 2 / genetics*
  • MicroRNAs / genetics*
  • Molecular Sequence Annotation
  • RNA, Circular / genetics*
  • RNA, Messenger / genetics

Substances

  • MIRN185 microRNA, human
  • MIRN423 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger
  • MMP2 protein, human
  • Matrix Metalloproteinase 2