Weighted gene co-expression network analysis to identify microRNAs functional modules and gene networks of heart failure with preserved ejection fraction
Objective To screen for potential biomarkers and therapeutic targets for heart failure with preserved ejection fraction(HFpEF)through bioinformatics analysis.Methods The microarray dataset GSE53437 was downloaded from the NCBI Gene Expression Omnibus.Weighted gene co-expression network analysis(WGCNA)was performed to identify gene modules and hub microRNAs(miRNAs)associated with HFpEF.Potential downstream target genes of miRNAs were predicted by miRNet.Gene Ontology(GO)annotation and KEGG pathway enrichment analysis for target genes were conducted via R package"ClusterProfiler".Protein-protein interaction(PPI)and miRNA-mRNA networks were constructed using the STRING database and Cytoscape software.Results The brown module showed the top positive correlation with HFpEF(r=0.37,P=3e-4).The brown module possessed the highest gene significance(GS)values.The intramodular analysis demonstrated a close relationship between module membership(MM)and GS of the brown module(r=0.61,P=7e-52).A total of 17 hub genes with MM＞0.85 and GS＞0.40 were identified as highly associated with HFpEF.A total of 1 578 target mRNAs were predicted by the miRNet database.GO annotation analysis revealed that these genes were involved in the following biological processes:the regulation of hematopoiesis,activation of T cells,and the modulation of cellular component size.Cellular components implicated in these processes included the transcription regulator complex,transport vesicles,and early endosomes.In terms of molecular functions,there was a significant enrichment in activities such as DNA-binding transcription repress or activity/RNA polymerase Ⅱ specificity,ubiquitin-protein ligase binding,and growth factor activity.KEGG pathway analysis indicated a substantial enrichment of these genes in signaling pathways,notably the Hippo,ErbB,TNF-α,and Ras signaling pathways.The regulatory network of miRNA-mRNA showed that miRNA-3188 interacted with UBA52,HDAC2,PSMF1 and SUFU;miRNA-3909 interacted with HDAC2,PSMF1,SUFU and RELA;miRNA-762 interacted with PSMF1,SUFU and RELA;miRNA548b-3p interacted with UBA52,HDAC2 and PSMF1;and miRNA-3198 interacted with UBA52,PSMF1,SUFU and RELA.Conclusion These findings may contribute to the interpretation of the underlying molecular mechanisms,as well as the identification of biomarkers and potential therapeutic targets for HFpEF.
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