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Published on: August 16, 2019
Identification of functional lncRNAs through constructing a lncRNA-associated ceRNA network in myocardial infarction
Beibei Zhu1, Yue Mao1, Mei Li1
1Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Insights
This study constructed a competing endogenous RNA (ceRNA) network to identify crucial long noncoding RNAs (lncRNAs) in myocardial infarction (MI). Three lncRNAs were identified as potential biomarkers for MI diagnosis and therapy.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Bioinformatics
Background:
- Myocardial infarction (MI) is ischemic necrosis of heart muscle, a critical aspect of coronary heart disease.
- The role of long noncoding RNAs (lncRNAs) in MI pathogenesis remains incompletely understood.
- Competing endogenous RNA (ceRNA) networks offer a framework for studying regulatory interactions.
Purpose of the Study:
- To construct a scale-free lncRNA-associated ceRNA network to identify key lncRNAs in MI.
- To explore the functional roles and potential biomarker significance of lncRNAs in MI.
- To uncover novel diagnostic and therapeutic targets for MI through ceRNA network analysis.
Main Methods:
- Construction of a scale-free lncRNA-associated ceRNA network.
- Identification of hub subnetworks and functional modules within the ceRNA network.
- Network centrality analysis and enrichment analysis of identified modules.
- Validation of miRNA and mRNA functions in MI-related biological processes.
Main Results:
- Disease genes for MI were significantly central in the constructed ceRNA network.
- Identified 2 MI-related functional modules, indicating lncRNA involvement in local network functions.
- Three crucial MI-related lncRNAs (CTD-3092A11.2, RP5-821D11.7, CTC-523E23.1) were identified as potential biomarkers.
- A total of 20 functional lncRNAs were identified, suggesting their roles in MI progression.
Conclusions:
- lncRNAs play significant roles in MI pathogenesis through ceRNA networks.
- The identified lncRNAs, particularly CTD-3092A11.2, RP5-821D11.7, and CTC-523E23.1, show promise as diagnostic and therapeutic biomarkers for MI.
- This study provides novel insights into ceRNA networks for understanding and potentially treating MI.
Abstract:
Myocardial infarction (MI) is a type of coronary heart disease, which refers to the ischemic necrosis of the heart muscle. A large number of studies have discussed the mechanism of MI from the perspective of competing endogenous RNA (ceRNA) network. However, the mechanisms underlying the function of lncRNAs in MI have still not been explained in an explicit manner. Therefore, we constructed a scale-free lncRNA-associated ceRNA network to identify some crucial lncRNAs in MI. Results showed that the given disease genes for MI were involved in the network, the degrees of which were significantly larger than the other nodes of the network. For measuring the network centrality, we then constructed a hub subnetwork. The miRNAs and mRNAs in the hub subnetwork have been validated to function in MI-related biological function. In addition, we identified 2 MI-related functional modules from the lncRNA-associated ceRNA network, which suggested that lncRNA exerted function in local network. Enrichment analysis showed that these functional modules corresponded to some similar and different pathways related to cardiovascular disease. More importantly, 3 MI-related crucial lncRNAs, CTD-3092A11.2, RP5-821D11.7 and CTC-523E23.1 were detected as potential biomarkers, which may be involved in MI-related biological progresses. Our study identified 20 functional lncRNAs based on ceRNA network analysis, which may provide novel diagnosis and therapeutic targets for MI from the ceRNA network perspective.
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