Dataset Information

Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease.

ABSTRACT:

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 H19, SNHG3 and ZNF436-AS1 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.

SUBMITTER: Chen L

PROVIDER: S-EPMC9315639 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundA growing body of evidence indicates that long non-coding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) to bind to microRNAs (miRNAs), thereby affecting and regulating the expression of target genes. The lncRNA-miRNA-mRNA ceRNA network has been theorized to play an indispensable role in many types of tumors. However, the role of the lncRNA-related ceRNA regulatory network in lung adenocarcinoma (LUAD) remains unclear.MethodsWe downloaded the RNAseq and miRNAseq data of LUAD from The Cancer Genome Atlas (TCGA) data portal and identified differentially expressed lncRNAs (DElncRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) between LUAD and corresponding paracancerous tissues by using the edgeR package of R software. We constructed the lncRNA-miRNA-mRNA ceRNA network by using Cytoscape (version 3.7.2) on the basis of the interaction generated from the miRcode, miRTarBase, miRDB, and TargetScan databases. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed with DAVID 6.8 bioinformatics resources and plotted by using the ggplot2 package in R. The effect of genes on LUAD prognosis was assessed by applying the survival package in R in accordance with the Kaplan-Meier curve.ResultsIn total, 1645 DElncRNAs, 117 DEmiRNAs, and 2729 DEmRNAs were identified in LUAD. The LUAD-specific ceRNA network was composed of 157 nodes and 378 edges (329 DElncRNA-DEmiRNA interactions and 49 DEmiRNA-DEmRNA interactions). GO and KEGG pathway annotations suggested that the LUAD-specific ceRNA network was related to tumor-related molecular functions and pathways. Seven lncRNAs (DISC1-IT1, SYNPR-AS1, H19, LINC00460, LINC00518, DSCR10, and STEAP2-AS1), one miRNA (hsa-mir-31), and 16 mRNAs (ATAD2, OSCAR, KIF23, E2F7, PFKP, MCM4, CEP55, CBX2, CCNE1, CLSPN, CCNB1, CDC25A, EZH2, CHEK1, SLC7A11, and PBK) were revealed to be significantly correlated with overall survival.ConclusionIn this study, we described the potential regulatory mechanism of the progression of LUAD. We proposed a new lncRNA-miRNA-mRNA ceRNA network that could help further explore the molecular mechanisms of LUAD.