A novel lncRNA-miRNA-mRNA triple network identifies lncRNA TWF1 as an important regulator of miRNA and gene expression i
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RESEARCH
Open Access
A novel lncRNA-miRNA-mRNA triple network identifies lncRNA TWF1 as an important regulator of miRNA and gene expression in coronary artery disease Liu Miao1, Rui-Xing Yin1,2,3* , Qing-Hui Zhang1, Xi-Jiang Hu1, Feng Huang1,2,3, Wu-Xian Chen1, Xiao-Li Cao2,3,4 and Jin-Zhen Wu1
Abstract 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 -miR142-3p was 0.856 and hsa -miR126-5p was 0.822. After the pairwise comparison, we found that TWF1 had significant statistical significance (PTWF1–142 < 0.05 and PTWF1–126 < 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. Keywords: Coronary artery disease, LncRNA-miRNA-mRNA regulators, Triple network analyses, Function enrichment, Biomarker of diagnosis
* Correspondence: [email protected] 1 Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi, People’s Republic of China 2 Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Disease Control and Prevention, 6 Shuangyong Road, Nanning 530021, Guangxi, People’s Republic of China Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Dom
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