A novel circRNA-miRNA-mRNA network identifies circ-YOD1 as a biomarker for coronary artery disease

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.

Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story

“…Several other specific conditions, such as coronary artery disease and nonvalvular persistent atrial fibrillation, have been associated with circRNAs, suggesting, respectively, that circ-YOD1 is a potential biomarker [ 124 ] and that circRNA002085 and circRNA001321 show evidence of circRNA-associated ceRNA mechanisms [ 125 ].…”

CircSND1 Regulated by TNF-α Promotes the Migration and Invasion of Cervical Cancer Cells

“…pathway. 27 To identify possible candidates that mediate the effects of miR-125a-3p in CC cells, we predicted with Targetscan (http://www.targetscan.org) and selected a target protein, FUT6, which contained conserved target sites of miR-125a-3p ( Figure 4A). We constructed the EGFP reporter plasmids containing 3′ UTR of FUT6.…”

Circular RNAs in Cardiac Regeneration: Cardiac Cell Proliferation, Differentiation, Survival, and Reprogramming

“…CircRNAs have been detected in peripheral fluids such as whole blood and plasma, where their increased chemical stability may be an advantage for their use as clinical biomarkers of diseases ( Gurha, 2019 ). A study from 2019 established a circRNA-miRNA-mRNA network and identified circYOD-1 as a circulating biomarker for coronary artery disease ( Miao et al, 2019 ). A study by Wu et al (2019) identified three differentialy regulated circRNAs in pediatric patients with congenital heart disease: hsa_circRNA_004183, hsa_circRNA_079265 and hsa_circRNA_105039.…”