Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease
Background: The high morbidity and mortality of calcific aortic valve disease (CAVD) represents an unmet clinical need to investigate the molecular mechanisms involved. Evidence suggests that long non-coding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) by binding to microRNAs and r...
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MDPI AG
2022-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/14/2204 |
| _version_ | 1797406962014486528 |
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| author | Long Chen Ke Wei Jun Li Yue Li Huiqing Cao Zhe Zheng |
| author_facet | Long Chen Ke Wei Jun Li Yue Li Huiqing Cao Zhe Zheng |
| author_sort | Long Chen |
| collection | DOAJ |
| description | Background: The high morbidity and mortality of calcific aortic valve disease (CAVD) represents an unmet clinical need to investigate the molecular mechanisms involved. Evidence suggests that long non-coding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) by binding to microRNAs and regulating target genes in cardiovascular diseases. Nevertheless, the role of lncRNAs related ceRNA regulation in CAVD remains unclear. Methods: RNAseq data of human diseased aortic valves were downloaded from GEO data sets (GSE153555, GSE199718), and differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs) between CAVD and non-calcific aortic valve tissues with limma R package. Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Set Enrichment analysis (GSEA) were performed with clusterProfiler and gesaplot2 R package. The pivotal microRNAs were predicted by three databases intersection including TargetScan, MiRwalk, miRDB according to the genes related to the crucial pathways. ENCORI was used to predict targeted lncRNAs of hub microRNAs. We constructed lncRNA-miRNA-mRNA ceRNA network with Cytoscape software. The lncRNAs in ceRNA network were verified by RT-qPCR in human 30 calcific and 20 noncalcified aortic valve tissues. Results: In total, 1739 DEmRNAs and 266 DElncRNAs were identified in CAVD. GO, KEGG pathway, GSEA annotations suggested that most of these genes are enriched in extracellular matrix (ECM)-reporter interaction pathways. The ceRNA networks associated with ECM-reporter interaction are constructed and related lncRNAs including <i>H19</i>, <i>SNHG3</i> and <i>ZNF436-AS1</i> were significant upregulated in human calcific aortic valve tissues, which might be potential therapeutic targets for CAVD. Conclusions: In this study, we proposed a novel lncRNA-miRNA-mRNA ceRNA network related to ECM-reporter interaction pathways, which potentially regulates CAVD progression. |
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| last_indexed | 2024-03-09T03:34:22Z |
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| spelling | doaj.art-34b7261d6f5943ad95ee1901e082a5db2023-12-03T14:49:56ZengMDPI AGCells2073-44092022-07-011114220410.3390/cells11142204Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve DiseaseLong Chen0Ke Wei1Jun Li2Yue Li3Huiqing Cao4Zhe Zheng5State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, ChinaState Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, ChinaState Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, ChinaState Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, ChinaLaboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100084, ChinaState Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, ChinaBackground: The high morbidity and mortality of calcific aortic valve disease (CAVD) represents an unmet clinical need to investigate the molecular mechanisms involved. Evidence suggests that long non-coding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) by binding to microRNAs and regulating target genes in cardiovascular diseases. Nevertheless, the role of lncRNAs related ceRNA regulation in CAVD remains unclear. Methods: RNAseq data of human diseased aortic valves were downloaded from GEO data sets (GSE153555, GSE199718), and differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs) between CAVD and non-calcific aortic valve tissues with limma R package. Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Set Enrichment analysis (GSEA) were performed with clusterProfiler and gesaplot2 R package. The pivotal microRNAs were predicted by three databases intersection including TargetScan, MiRwalk, miRDB according to the genes related to the crucial pathways. ENCORI was used to predict targeted lncRNAs of hub microRNAs. We constructed lncRNA-miRNA-mRNA ceRNA network with Cytoscape software. The lncRNAs in ceRNA network were verified by RT-qPCR in human 30 calcific and 20 noncalcified aortic valve tissues. Results: In total, 1739 DEmRNAs and 266 DElncRNAs were identified in CAVD. GO, KEGG pathway, GSEA annotations suggested that most of these genes are enriched in extracellular matrix (ECM)-reporter interaction pathways. The ceRNA networks associated with ECM-reporter interaction are constructed and related lncRNAs including <i>H19</i>, <i>SNHG3</i> and <i>ZNF436-AS1</i> were significant upregulated in human calcific aortic valve tissues, which might be potential therapeutic targets for CAVD. Conclusions: In this study, we proposed a novel lncRNA-miRNA-mRNA ceRNA network related to ECM-reporter interaction pathways, which potentially regulates CAVD progression.https://www.mdpi.com/2073-4409/11/14/2204long non-coding RNAscompetitive endogenous RNA networksbioinformaticscalcific aortic valve disease |
| spellingShingle | Long Chen Ke Wei Jun Li Yue Li Huiqing Cao Zhe Zheng Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease Cells long non-coding RNAs competitive endogenous RNA networks bioinformatics calcific aortic valve disease |
| title | Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease |
| title_full | Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease |
| title_fullStr | Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease |
| title_full_unstemmed | Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease |
| title_short | Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease |
| title_sort | integrated analysis of lncrna mediated cerna network in calcific aortic valve disease |
| topic | long non-coding RNAs competitive endogenous RNA networks bioinformatics calcific aortic valve disease |
| url | https://www.mdpi.com/2073-4409/11/14/2204 |
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