Construction of Immune-Related circRNA-miRNA-mRNA Network and Identification of circRNAs as Biomarkers in Coronary Atherosclerotic Heart Disease

Abstract

Circular RNAs (circRNAs) play crucial roles in the immune and inflammatory responses of many diseases by acting as competing endogenous RNAs (ceRNAs). However, the role of circRNAs as ceRNAs in the immune and inflammatory processes of coronary atherosclerosis heart disease (CHD) remains unclear. This study aimed to identify and validate the potential immune-related circRNAs as biomarkers for CHD. Firstly, we constructed a ceRNA regulatory network including 14 circRNAs, 24 miRNAs, and 15 genes through bioinformatics analysis. Four hub genes were identified and five candidate immune-related circRNAs were screened. Subsequently, the expression levels of these candidate circRNAs were detected by qRT-PCR. Notably, hsa_circRNA_101069 and hsa_circRNA_406053 showed significant up-regulation in CHD patients (p < 0.001). The value of these circRNAs as biomarkers for CHD was evaluated by the area under the ROC curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indexes. Adding circRNAs to a traditional CHD model significantly enhanced classification performance, with an IDI of 0.058 and an NRI of 0.280 for hsa_circRNA_101069 and an IDI of 0.051 and an NRI of 0.480 for hsa_circRNA_406053. Furthermore, hsa_circRNA_101069 was up-regulated in ox-LDL-induced THP-1 macrophages, and silencing hsa_circRNA_101069 significantly inhibited the apoptosis rates and the inflammatory cytokines levels. This study constructed an immune-related circRNA-miRNA-mRNA network and identified two circRNAs as biomarkers for CHD, with hsa_circRNA_101069 potentially contributing to the pathological basis of CHD.

Keywords

• circular RNA
• coronary atherosclerosis heart disease
• biomarker
• immune inflammation
• regulatory network