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Construction of a circRNA-Mediated ceRNA Network Reveals Novel Biomarkers for Aortic Dissection
De-Bin Liu1, You-Fu He2,3,4, Gui-Jian Chen1
1Department of Cardiology, The Second People's Hospital of Shantou, Shantou, Guangdong Province, People's Republic of China.
Insights
This study reveals altered circRNA-associated competing endogenous RNA (ceRNA) networks in aortic dissection (AD). These findings suggest circRNAs are crucial in AD development and could be potential diagnostic biomarkers.
Area of Science:
- Molecular Biology
- Genetics
- Cardiovascular Research
Background:
- Aortic dissection (AD) is a life-threatening condition with an unknown genetic basis.
- Circular RNAs (circRNAs) are implicated in various biological processes, but their role in AD remains unexplored.
- Understanding circRNA regulation is crucial for elucidating AD pathogenesis.
Purpose of the Study:
- To investigate the role of circRNAs in AD by analyzing the circRNA-associated competing endogenous RNA (ceRNA) network.
- To identify differentially expressed RNAs (DERNAs) involved in AD.
- To construct and analyze a circRNA-miRNA-mRNA ceRNA network in AD.
Main Methods:
- Downloaded circRNA, miRNA, and mRNA expression profiles from Gene Expression Omnibus (GEO) databases.
- Identified DERNAs using bioinformatics analysis and confirmed key molecules via qRT-PCR.
- Constructed a circRNA-miRNA-mRNA ceRNA network and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
Main Results:
- Identified 14 differentially expressed circRNAs, 17 differentially expressed miRNAs, and 527 differentially expressed mRNAs.
- KEGG analysis revealed associations with focal adhesion and extracellular matrix receptor interaction pathways.
- A ceRNA network involving hsa_circRNA_082317, hsa-miR-149-3p, and 10 mRNAs was constructed. qRT-PCR confirmed upregulation of hsa_circRNA_082317 and ITGA5, and downregulation of hsa-miR-149-3p in AD.
Conclusions:
- This is the first study to demonstrate alterations in the circRNA-associated ceRNA network in AD.
- CircRNAs likely play significant roles in the onset and progression of AD.
- CircRNAs may serve as potential biomarkers for AD diagnosis and treatment.
Background:
Aortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circRNAs play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in AD based on the circRNA-associated competing endogenous RNA (ceRNA) network.
Methods:
Expression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified by bioinformatics analysis. CircRNA-miRNA-mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of circRNA-associated ceRNA network. RNA was isolated from human arterial blood samples after which qRT-PCR was performed to confirm the DERNAs.
Results:
We identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) (adjusted P-value <0.05 and | log2FC | > 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix receptor interaction signaling pathways. Simultaneously, the present study constructed a ceRNA network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1). qRT-PCR demonstrated that hsa_circRNA_082317 and ITGA5 were significantly up-regulated, and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3).
Conclusion:
This is the first study to demonstrate the circRNA-associated ceRNA network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression and thus may serve as potential biomarkers for the diagnosis and treatment of AD.
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