A novel lncRNA-miRNA-mRNA triple network identifies lncRNA TWF1 as an important regulator of miRNA and gene expression in coronary artery disease

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in numerous physiological functions. Yet, their mechanisms in coronary artery disease (CAD) are not well understood. METHODS: The expression profile of genes associated to CAD was reannotated into the lncRNA-mRNA biphasic profile. The target microRNA data were used to design a global CAD triple network. Thereafter, we conducted a functional enrichment analysis and clustering using the triple network from the level of topology analyses. The expression of four non-coding RNAs (ncRNAs) was measured by qRT-PCR and the risk of CAD was calculated by nomogram. The prognostic value of three ncRNAs was evaluated using receiver operating characteristic (ROC) curve. RESULTS: A CAD lncRNA-miRNA-mRNA network was constructed which included 15 mRNAs, 3 miRNAs, 19 edges and one lncRNA. Nomogram showed that four ncRNAs were the risk of CAD. After RT-PCR validation in four ncRNAs between CAD and non-CAD samples, only three ncRNAs had significant meaning for further analysis. ROC curve showed that TWF1 presented an area under curve (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 had significant statistical significance (P(TWF1–142) < 0.05 and P(TWF1–126) < 0.01). The results of functional enrichment analysis of interacting gene and microRNA showed that the shared lncRNA TWF1 may be a new factor for CAD. CONCLUSIONS: This investigation on the regulatory networks of lncRNA-miRNA-mRNA in CAD suggests that a novel lncRNA, lncRNA TWF1 is a risk factor for CAD, and expands our understanding into the mechanisms involved in the pathogenesis of CAD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12986-019-0366-3) contains supplementary material, which is available to authorized users.