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Updated: Oct 2, 2025
In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
Published on: October 21, 2022
Construction of a circRNA-miRNA-mRNA Regulatory Network for Coronary Artery Disease by Bioinformatics Analysis
Zebo Zhang1, Haiyan Qian1, Li Wang2
1Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang Province 315211, China.
Insights
This study reveals a circRNA-miRNA-mRNA network in coronary artery disease (CAD), identifying key genes involved in ubiquitin-mediated proteolysis. These findings suggest potential diagnostic biomarkers and therapeutic targets for CAD.
Area of Science:
- Molecular Biology
- Genomics
- Biochemistry
Background:
- Circular RNAs (circRNAs) are implicated in various disease pathogenetic mechanisms.
- The specific role of circRNAs in coronary artery disease (CAD) pathogenesis remains largely unexplored.
- Competing endogenous RNA (ceRNA) networks involving circRNAs are crucial regulatory mechanisms.
Purpose of the Study:
- To construct a circRNA-related competing endogenous RNA (ceRNA) network in coronary artery disease (CAD).
- To identify key circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) involved in CAD pathogenesis.
- To elucidate the potential biological functions and pathways associated with circRNAs in CAD.
Main Methods:
- Utilized Gene Expression Omnibus datasets for CAD gene expression profiles.
- Performed bioinformatics analysis to construct a ceRNA regulatory network.
- Employed protein-protein interaction (PPI) networks to identify hub genes and construct a circRNA-miRNA-hub gene subnetwork.
- Conducted function enrichment analysis to explore underlying biological mechanisms.
Main Results:
- Identified 115 differentially expressed circRNAs (DEcircRNAs), 17 differentially expressed miRNAs (DEmiRNAs), and 790 differentially expressed mRNAs (DEmRNAs) in CAD.
- Constructed a comprehensive circRNA-miRNA-mRNA regulatory network.
- Identified a significant circRNA-miRNA-hub gene subnetwork involving nine circRNAs, four miRNAs, and eight hub genes (e.g., MKRN1, UBE2H, SIAH2).
- Found hub genes enriched in the ubiquitin-mediated proteolysis pathway, suggesting its role in CAD pathogenesis.
Conclusions:
- The study establishes a circRNA-miRNA-mRNA regulatory network relevant to CAD.
- Identified specific circRNAs, miRNAs, and mRNAs that may serve as novel diagnostic biomarkers for CAD.
- These findings highlight potential therapeutic targets for managing coronary artery disease.
Background:
Circular RNAs (circRNAs) were known to be related to the pathogenesis of many diseases through competing endogenous RNA (ceRNA) regulatory mechanisms. However, the function of circRNA in coronary artery disease (CAD) remains unclear. In this study, we aim to construct a circRNA-related competing endogenous RNA (ceRNA) network in CAD.
Methods:
The gene expression profiles of CAD were obtained from Gene Expression Omnibus datasets. Bioinformatics analysis was performed to construct a ceRNA regulatory network, from which the hub genes involved were identified through protein-protein interaction (PPI) networks leading to the identification of the circRNA-miRNA-hub gene subnetwork. In addition, function enrichment analysis was performed to detect the potential biological mechanism in which circRNA might be involved.
Results:
A total of 115 DEcircRNAs (differentially expressed circRNAs), 17 DEmiRNAs (differentially expressed microRNAs), and 790 DEmRNAs (differentially expressed mRNAs) were identified between CAD and control groups from microarray datasets. Functional enrichment analysis showed that DEmRNAs were significantly involved in inflammation-related pathways and ubiquitin-protein ligase binding. After identifying 20 DEcircRNA-DEmiRNA pairs and 561 DEmiRNA-DEmRNA pairs, we obtained a circRNA-miRNA-mRNA regulatory network. PPI network analysis showed that eight hub genes were closely related to CAD, leading to the identification of a circRNA-miRNA-hub gene subnetwork consisting of nine circRNAs (hsa_circ_0020275, hsa_circ_0020387, hsa_circ_0020417, hsa_circ_0045512, hsa_circ_0047336, hsa_circ_0069094, hsa_circ_0071326, hsa_circ_0071330, and hsa_circ_0085340), four miRNAs (hsa-miR-136-5p, hsa-miR-376c-3p, hsa-miR-411-5p, and hsa-miR-654-5p), and eight mRNAs (MKRN1, UBE2H, UBE2W, UBE2D1, UBE2F, BE2J1, ZNRF1, and SIAH2). In addition, we discovered these hub genes were enriched in the ubiquitin-mediated proteolysis pathway, suggesting circRNAs may be involved in the pathogenesis of CAD through this pathway.
Conclusions:
This study may deepen our understanding of the potential role of circRNA-miRNA-mRNA regulation network in CAD and suggest novel diagnostic biomarkers and therapeutic targets for CAD.
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