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Expression Profiles and Bioinformatic Analysis of Circular RNAs in Db/Db Mice with Cardiac Fibrosis
Lingling Yuan1, Ting Wang1, Jinsheng Duan2
1Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050004, People's Republic of China.
Introduction:
Cardiac fibrosis is one of the important causes of heart failure and death in diabetic cardiomyopathy (DCM) patients. Circular RNAs (circRNAs) are covalently closed RNA molecules in eukaryotes and have high stability. Their role in myocardial fibrosis with diabetic cardiomyopathy (DCM) remain to be fully elucidated. This study aimed to understand the expression profiles of circRNAs in myocardial fibrosis with DCM, exploring the possible biomarkers and therapeutic targets for DCM.
Methods:
At 21 weeks of age, db/db mice established the type 2 DCM model measured by echocardiography, and the cardiac tissue was extracted for Hematoxylin-eosin, Masson's trichrome staining, and transmission electron microscopy. Subsequently, the expression profile of circRNAs in myocardial fibrosis of db/db mice was constructed using microarray hybridization and verified by real-time quantitative polymerase chain reaction. A circRNA-microRNA-messenger RNA coexpression network was constructed, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were done.
Results:
Compared with normal control mice, db/db mice had 77 upregulated circRNAs and 135 downregulated circRNAs in their chromosomes (fold change ≥1.5, P ≤ 0.05). Moreover, the enrichment analysis of circRNA host genes showed that these differentially expressed circRNAs were mainly involved in mitogen-activated protein kinase signaling pathways. CircPHF20L1, circCLASP1, and circSLC8A1 were the key circRNAs. Moreover, circCLASP1/miR-182-5p/Wnt7a, circSLC8A1/miR-29b-1-5p/Col12a1, and most especially circPHF20L1/miR-29a-3p/Col6a2 might be three novel axes in the development of myocardial fibrosis in DCM.
Conclusion:
The findings will provide some novel circRNAs and molecular pathways for the prevention or clinical treatment of DCM through intervention with specific circRNAs.
Insights
Diabetic cardiomyopathy (DCM) involves cardiac fibrosis. This study identified key circular RNAs (circRNAs) and molecular pathways in DCM, offering potential biomarkers and therapeutic targets for heart failure treatment.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genomics
Background:
- Cardiac fibrosis is a major cause of heart failure and mortality in diabetic cardiomyopathy (DCM).
- The role of circular RNAs (circRNAs) in myocardial fibrosis associated with DCM is not fully understood.
- Identifying novel molecular mechanisms is crucial for developing effective DCM therapies.
Purpose of the Study:
- To investigate the expression profiles of circRNAs in myocardial fibrosis in a type 2 diabetic cardiomyopathy (DCM) mouse model.
- To explore potential circRNA biomarkers for DCM diagnosis.
- To identify novel therapeutic targets for DCM by elucidating circRNA-mediated pathways.
Main Methods:
- Established a type 2 DCM mouse model (db/db mice) and performed cardiac tissue analysis (histology, electron microscopy).
- Utilized microarray hybridization to profile circRNA expression and real-time quantitative PCR for validation.
- Constructed a circRNA-microRNA-messenger RNA coexpression network and performed pathway enrichment analysis (GO, KEGG).
Main Results:
- Identified 77 upregulated and 135 downregulated circRNAs in DCM mice compared to controls.
- Differentially expressed circRNAs were significantly enriched in mitogen-activated protein kinase signaling pathways.
- Key circRNAs (circPHF20L1, circCLASP1, circSLC8A1) and novel regulatory axes (e.g., circPHF20L1/miR-29a-3p/Col6a2) were identified in DCM-related myocardial fibrosis.
Conclusions:
- This study reveals novel circRNAs and molecular pathways involved in DCM-induced myocardial fibrosis.
- Identified circRNAs and pathways may serve as potential biomarkers and therapeutic targets for DCM.
- Findings offer a basis for developing targeted interventions for DCM prevention and treatment.
