Identification of hsa_circ_0001445 of a novel circRNA-miRNA-mRNA regulatory network as potential biomarker for coronary heart disease

Abstract

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.

Circular RNAs Variously Participate in Coronary Atherogenesis

“…Being a sponge for miR-208b-5p, circ_0001445 has an atheroprotective effect by inhibiting ox-LDL-induced HUVEC inflammation, oxidative stress, apoptosis, and foam cell formation. New circRNA–miRNA–mRNA regulatory networks have recently been constructed for hsa_circ_0001445 [ 116 ]. Bioinformatics analysis revealed an association of hsa_circ_0001445 with three miRNAs (hsa-miR-507, hsa-miR-375-3p, and hsa-miR-942-5p).…”

“…The results of circRNA measurement with RT-PCR or RNA-Seq can be used for early diagnosis, treatment selection, disease prognosis, and treatment control [ 163 ]. The circRNA level can serve as a potential biomarker of CAD in different samples, such as: peripheral blood (has_circ_0124644) [ 165 ]; mononuclear cells (BTBD7_hsa_circ_0000563, hsa_circ_0001879, and has_circ_0004104) [ 47 , 166 ]; plasma and peripheral blood leukocytes (hsa_circ_0001445) [ 114 , 116 ]; and extracellular vesicles (hsa_circ_0005540) [ 167 ]. As can be seen from Table 1 and Table 2 , dozens of circRNAs are currently considered risk factors for the development of CAD, making them potential biomarkers and possible targets for the treatment of this pathology.…”