ObjectsTo evaluate the hsa_circ_0001445 level in peripheral blood leukocytes of patients with coronary heart disease (CHD) and its related clinical factors, and predict its circRNA-miRNA-mRNA regulatory network in CHD pathogenesis via bioinformatics analysis.MethodsPeripheral blood leukocytes were isolated from the whole blood samples of 94 CHD patients (aged 65.96 ± 9.78 years old) and 126 healthy controls (aged 60.75 ± 8.81 years old). qRT-PCR was used to quantify the expression level of circRNA and subsequently analyze its association with CHD clinical parameters. Via bioinformatics algorithm and GEO datasets, differential miRNA expression was evaluated using the Limma package. A miRNA-mRNA regulatory network was predicted by cyTargetLinker. ClusterProfiler was employed to perform functional enrichment analysis of the circRNA network to investigate its role in CHD pathogenesis.ResultsThe expression of hsa_circ_0001445 in peripheral blood leukocytes of CHD patients was downregulated compared with that of healthy controls. Positive correlations were evident between hsa_circ_0001445 expression level and the levels of hemoglobin, triglycerides, high- and low-density lipoprotein cholesterol. A significant negative correlation was also found between hsa_circ_0001445 expression level and age and the neutrophil level. Low expression of hsa_circ_0001445 exhibited a discriminatory ability between CHD patients and healthy controls with a sensitivity of 67.5% and a specificity of 76.6% (p < 0.05). By bioinformatics analysis, 405 gene ontology terms were identified. The Kyoto Encyclopedia of Genes and Genomes terms focused principally on the PI3K-Akt signaling pathway. hsa_circ_0001445 was associated with the expression of three miRNAs that may regulate 18 genes involved in KEGG processes: hsa-miR-507, hsa-miR-375–3p, and hsa-miR-942–5p.ConclusionThe hsa_circ_0001445 level in peripheral blood leukocytes may serve as a biomarker for CHD diagnosis. Our work on circRNA-miRNA-mRNA networks suggests a potential role for hsa_circ_0001445 in CHD development.
Background
Ischemic cardiomyopathy (ICM) has ranked as the most common cause morbidity and mortality in the elderly over the past decades. One of the most important reasons for this is that its exact underlying mechanism remains poorly understood.
Methods
Five datasets were downloaded from the GEO database. Differential gene expression (DGE) was identified by the R RobustRankAggreg package. Differential miRNA expression was evaluated by the Limma package. Gene potential functions were then determined by the clusterProfiler database. The miRNA-DGE regulatory network was predicted by cyTargetLinker. Then, a protein-protein interaction network was constructed by STRING tool, MCODE, and BiNGO tool.
Results
91 miRNAs and 274 potential genes were identified. Of these, COL1A1, IGF1 and CCND1 were found to be involved in many signaling pathways; and miR-9-5p was found to play critical roles in ICM.
Conclusion
Our study has unraveled the potential key genes and miRNAs as well as the possible underlying molecular pathogenesis of ICM, which is a crucial step leading to a new avenue for the early intervention of this disorder.
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