Abstract

BackgroundLong noncoding RNAs (lncRNAs) are involved in numerous physiological functions. However, their mechanisms in acute myocardial infarction (AMI) are not well understood.MethodsWe performed an RNA-seq analysis to explore the molecular mechanism of AMI by constructing a lncRNA-miRNA-mRNA axis based on the ceRNA hypothesis. The target microRNA data were used to design a global AMI triple network. Thereafter, a functional enrichment analysis and clustering topological analyses were conducted by using the triple network. The expression of lncRNA SNHG8, SOCS3 and ICAM1 was measured by qRT-PCR. The prognostic values of lncRNA SNHG8, SOCS3 and ICAM1 were evaluated using a receiver operating characteristic (ROC) curve.ResultsAn AMI lncRNA-miRNA-mRNA network was constructed that included two mRNAs, one miRNA and one lncRNA. After RT-PCR validation of lncRNA SNHG8, SOCS3 and ICAM1 between the AMI and normal samples, only lncRNA SNHG8 had significant diagnostic value for further analysis. The ROC curve showed that SNHG8 presented an AUC of 0.850, while the AUC of SOCS3 was 0.633 and that of ICAM1 was 0.594. After a pairwise comparison, we found that SNHG8 was statistically significant (PSNHG8-ICAM1 = 0.002; PSNHG8-SOCS3 = 0.031). The results of a functional enrichment analysis of the interacting genes and microRNAs showed that the shared lncRNA SNHG8 may be a new factor in AMI.ConclusionsOur investigation of the lncRNA-miRNA-mRNA regulatory networks in AMI revealed a novel lncRNA, lncRNA SNHG8, as a risk factor for AMI and expanded our understanding of the mechanisms involved in the pathogenesis of AMI.

Highlights

  • Long noncoding RNAs are involved in numerous physiological functions

  • Data preprocessing and identified differentially expressed genes After quality control, we found that the acute myocardial infarction (AMI) samples 4, 11, 22 and 31 could not be normalized (Fig. 2a), and we had to remove them from the analysis (Fig. 2b)

  • Functional annotation, Protein-protein interaction (PPI) network construction and identification of hub genes We used the clusterProfiler package in R to carry out the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology (DO) functional and Gene Ontology (GO) analyses to elucidate the role of Differentially expressed mRNAs (DEGs) (Fig. 4)

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Summary

Methods

We performed an RNA-seq analysis to explore the molecular mechanism of AMI by constructing a lncRNA-miRNA-mRNA axis based on the ceRNA hypothesis. The target microRNA data were used to design a global AMI triple network. Thereafter, a functional enrichment analysis and clustering topological analyses were conducted by using the triple network. The expression of lncRNA SNHG8, SOCS3 and ICAM1 was measured by qRT-PCR. The prognostic values of lncRNA SNHG8, SOCS3 and ICAM1 were evaluated using a receiver operating characteristic (ROC) curve

Results
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Background
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