A Novel lncRNA-miRNA-mRNA Triple Network Identifies lncRNA TWF1 as an Important Regulator of miRNA and Gene Expression in Coronary Artery Disease

Abstract

Background: Recent evidence has shown that some long non-coding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory mechanism of lncRNA in coronary artery disease (CAD) remains unclear. Methods: We reannotated the disease related to CAD gene expression profile into a lncRNA-mRNA biphasic profile and integrated the microRNA target data to construct a global CAD triple network. A further clustering and function enrichment analysis was performed on the triple network from the level of topology analyses. Quantitative real-time PCR was used to determine the expression of four non-coding RNAs (ncRNAs). Receiver operating characteristic (ROC) curve was performed to evaluate the prognostic value of three ncRNAs. Findings: We constructed a CAD lncRNA-miRNA-mRNA network including one lncRNAs, 3 miRNAs, 15 mRNAs and 19 edges. After RT-PCR validation in four ncRNAs between CAD and non-CAD samples, only three ncRNAs with significant meaning for further analysis. ROC curve showed that TWF1 presented an AUC of 0.862, the AUC of hsa -miR-142-3p was 0.856 and hsa -miR126-5p was 0.822. After the pairwise comparison, we found that TWF1 has significant statistical significance (PTWF1-142 < 0.05 and PTWF1-126 < 0.01). For the shared lncRNA TWF1, the interacting gene and microRNA functional enrichment studies implied that lncRNA TWF1 might function as a new regulator in CAD. Interpretation: This study focused on CAD lncRNA-miRNA-mRNA regulatory networks, and found that lncRNA TWF1 was a new CAD risk lncRNA, which might provide novel insight into a better understanding of the pathogenesis of CAD. Funding Statement: The authors acknowledge the essential role of the funding of the National Natural Science Foundation of China (No: 81460169) and the Innovation Project of Guangxi Graduate Education in this motif. Declaration of Interests: The authors have no potential conflicts of interest to report Ethics Approval Statement: The study design was approved by the Ethics Committee of the First Affiliated Hospital, Guangxi Medical University (No: Lunshen-2011-KY-Guoji-001; Mar. 7, 2011). All procedures were performed in accordance with ethical standards. Informed consent was obtained from all subjects after receiving a full explanation of the study.