Abstract
BackgroundHeart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure development also are largely unknown. Using published Gene Expression Omnibus (GEO) datasets, in the present study, we aim to comprehensively analyze the differentially expressed genes in failing heart tissues, and identified the critical signaling pathways and transcription factors involving heart failure development.MethodsThe transcriptional profiling of heart failure was identified from previously published gene expression datasets deposited in GSE5406, GSE16499 and GSE68316. The enriched signaling pathways and transcription factors were analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) website and gene set enrichment analysis (GSEA) assay. The transcriptional networks were created by Cytoscape.ResultsCompared with the normal heart tissues, 90 genes were particularly differentially expressed in failing heart tissues, and those genes were associated with multiple metabolism signaling pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in failing heart tissues. Transcription factors MYC and C/EBPβ were both negatively associated with the expression profiling of failing heart tissues in GSEA assay. Moreover, compared with normal heart tissues, MYC and C/EBPβ were down regulated in failing heart tissues. Furthermore, MYC and C/EBPβ mediated downstream target genes were also decreased in failing heart tissues. MYC and C/EBPβ were positively correlated with each other. At last, we constructed MYC and C/EBPβ mediated regulatory networks in failing heart tissues, and identified the MYC and C/EBPβ target genes which had been reported involving the heart failure developmental progress.ConclusionsOur results suggested that metabolism pathways and insulin signaling pathway, transcription factors MYC and C/EBPβ played critical roles in heart failure developmental progress.
Highlights
Heart failure is one of leading cause of death worldwide
Through gene set enrichment analysis (GSEA) analysis, we found that the insulin signaling pathway was negatively correlated with the failing heart expression profiling (Fig. 3c), suggesting the inactivation of insulin signaling pathway in the development of heart failure
We found that C/EBPβ expression was positively correlated with MYC expression
Summary
Heart failure is one of leading cause of death worldwide. The transcriptional profiling of heart failure is unclear. The signaling pathways and transcription factors involving the heart failure development are largely unknown. Using published Gene Expression Omnibus (GEO) datasets, in the present study, we aim to comprehensively analyze the differentially expressed genes in failing heart tissues, and identified the critical signaling pathways and transcription factors involving heart failure development. Heart failure is a rapidly growing public health issue and one of leading cause of death [1]. Transcriptional genomics results revealed that FOX families of transcription factors were associated with human heart failure [4]. The mis-regulated molecular signaling pathways and key transcription factors in heart failure are largely unknown
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