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Published on: February 24, 2017
Analysis of changes in circular RNA expression and construction of ceRNA networks in human dilated cardiomyopathy
Zhenhao Lin1,2, Yongchao Zhao1,2, Fangjie Dai1,2
1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Insights
Circular RNAs (circRNAs) show altered expression in dilated cardiomyopathy (DCM) patients. This study identifies key circRNAs and constructs networks, offering new insights into DCM mechanisms.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Epigenetics
Background:
- Dilated cardiomyopathy (DCM) is a severe, life-threatening heart condition with unclear underlying mechanisms.
- Circular RNAs (circRNAs) are implicated in cardiovascular diseases, potentially acting as competitive endogenous RNAs (ceRNAs).
- The specific role of circRNAs in human DCM remains largely unelucidated.
Purpose of the Study:
- To identify differentially expressed circRNAs in human DCM.
- To explore the potential functions of these circRNAs in DCM pathogenesis.
- To construct circRNA-miRNA-mRNA networks based on ceRNA theory.
Main Methods:
- RNA sequencing of heart samples from DCM patients and healthy controls.
- Validation of differentially expressed circRNAs and mRNAs using qRT-PCR.
- Bioinformatic analysis including ceRNA network construction, GO, and KEGG pathway analysis.
Main Results:
- Identification of 9585 circRNAs and 22050 mRNAs.
- Significant up-regulation of 213 circRNAs and 617 mRNAs in DCM hearts.
- Significant down-regulation of 85 circRNAs and 1125 mRNAs in DCM hearts.
- Construction of two circRNA-miRNA-mRNA networks.
Conclusions:
- Cardiac circRNA expression is significantly altered in human DCM.
- circRNAs may play a crucial role in DCM development through ceRNA mechanisms.
- This study provides a foundation for further research into circRNAs as potential therapeutic targets for DCM.
Abstract:
Dilated cardiomyopathy (DCM) is a severe life-threatening disease worldwide, and the underlying mechanisms remain unclear. Circular RNAs (circRNAs) have been reported to play important roles in various cardiovascular diseases and can function as competitive endogenous RNAs (ceRNAs). However, their role in human DCM has not been fully elucidated. In the present study, heart samples from DCM patients and healthy controls were used to identify circRNAs by RNA sequencing. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to validate differentially expressed circRNAs and mRNAs. A total of 9585 circRNAs and 22050 mRNAs were detected in the two groups. Overall, 213 circRNAs and 617 mRNAs were significantly up-regulated in the DCM group compared with the control group. Similarly, 85 circRNAs and 1125 mRNAs were significantly down-regulated. According to the ceRNA theory, circRNAs can indirectly interact with mRNAs by directly binding to microRNAs (miRNAs), and circRNAs and mRNAs should be concurrently either up-regulated or down-regulated. Based on this theory, we constructed two circRNA-miRNA-mRNA networks by using the RNA sequencing data and prediction by proprietary software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to probe the potential functions of differentially expressed circRNAs. In conclusion, this study revealed that the expression of cardiac circRNAs was altered in human DCM and explored the potential functions of circRNAs by constructing ceRNA networks. These findings provide a foundation for future studies of circRNAs in DCM.
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