Abstract
Circular RNAs (circRNAs) are involved in many physiological functions. Whether circulating circRNAs serve as markers for coronary artery disease (CAD) is unknown. Seven CAD-related microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed using clustering and functional enrichment to identify hub mRNAs and miRNAs. StarBase V3.0 and circinteractome databases were used to predict interactions between circRNAs and miRNAs whereas miRwalk and DIANA TOOLS were used to predict interactions between miRNAs and mRNAs. Altogether, this helped establish a circRNA-miRNA-mRNA triple network for diagnosis of CAD. Five non-coding RNAs (ncRNAs) were identified in our study population with the use of quantitative real-time PCR (RT-PCR). The prognostic values of circYOD1, hsa-miR-21-3p and hsa-miR-296-3p were evaluated using a receiver operating characteristic (ROC) curve. A CAD circRNA-miRNA-mRNA network was established from our analyses containing one circRNA, four miRNAs and thirteen mRNAs. After performing RT-PCR validation between CAD and non-CAD samples, only three ncRNAs of five ncRNAs showed significance for further analysis. The area under ROC curve (AUC) of circ-YOD1 was 0.824, the AUC of hsa-miR-21-3p was 0.731 and hsa-miR-296-3p was 0.776. The pairwise comparison results showed that circ-YOD1 had statistical significance (PYOD1-21 < 0.01 and PYOD1-296 < 0.05). The results of functional enrichment analysis of interacting genes and microRNAs showed that the shared circ-YOD1 may act as a new biomarker for CAD. Our investigation of the triple regulatory networks of circRNA-miRNA-mRNA in CAD revealed circ-YOD1 as a potential biomarker for CAD.
Highlights
Coronary artery disease (CAD), a complex and multifactorial disorder, remains one of the most common causes of death and results in a heavy economic and social burden worldwide[1]
After quality control and elimination of incorrect expression data, we identified a total of 250 DEGs, including 144 that were upregulated and 106 downregulated DEGs in coronary artery disease (CAD) samples as compared to control samples
GSE34198 consisted of the DEGs CHRM1, FBXL18, FGF2, GPR17 and IL1A; GSE60993 consisted of MMP9, FCGR3B and GZMK; and GSE61144 consisted of BCL6, GZMA, MZMK, MMP9, EOMES and IL2RB
Summary
Coronary artery disease (CAD), a complex and multifactorial disorder, remains one of the most common causes of death and results in a heavy economic and social burden worldwide[1]. If there was a biomarker that can be measured in peripheral blood, it can be used for early detection of those at high-risk for CAD, which will help prevent and treat the disease[6]. Peripheral blood biochemical tests are only valuable for assessing the risk factors of CAD These examinations usually show significant changes in severe complications, such as acute coronary syndrome. Previous studies have shown that circRNAs may modify parental gene expression through their function as microRNA (miRNA) sponges[10]. This way, circRNAs play an important role in the pathogenesis and progression of CAD, which deserves in-depth investigation[11].
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