Abstract
Atherosclerosis, a multifactorial and chronic immune inflammatory disorder, is the main cause of multiple cardiovascular diseases. Researchers recently reported that lncRNAs may exert important functions in the progression of atherosclerosis (AS). Some studies found that lncRNAs can act as ceRNAs to communicate with each other by the competition of common miRNA response elements. However, lncRNA-associated ceRNA network in terms of atherosclerosis is limited. In present study, we pioneered to construct and systematically analyze the lncRNA-mRNA network and reveal its potential roles in carotid atherosclerotic rabbit models. Atherosclerosis was induced in rabbits (n = 3) carotid arteries via a high-fat diet and balloon injury, while age-matched rabbits (n = 3) were treated with normal chow as controls. RNA-seq analysis was conducted on rabbits carotid arteries (n = 6) with or without plaque formation. Based on the ceRNA mechanism, a ternary interaction network including lncRNA, mRNA, and miRNA was generated and an AS-related lncRNA-mRNA network (ASLMN) was extracted. Furthermore, we analyzed the properties of ASLMN and discovered that six lncRNAs (MSTRG.10603.16, 5258.4, 12799.3, 5352.1, 12022.1, and 12250.4) were highly related to AS through topological analysis. GO and KEGG enrichment analysis indicated that lncRNA MSTRG.5258.4 may downregulate inducible co-stimulator to perform a downregulated role in AS through T cell receptor signaling pathway and downregulate THBS1 to conduct a upregulated function in AS through ECM-receptor interaction pathway. Finally, our results elucidated the important function of lncRNAs in the origination and progression of AS. We provided an ASLMN of atherosclerosis development in carotid arteries of rabbits and probable targets which may lay the foundation for future research of clinical applications.
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Present research was supported by the National Natural Science Foundation of China (No. 81671689) and the Natural Science Foundation of Heilongjiang Province (H2017021).
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All performed procedures involved in this study were endorsed by the Medical Ethics Committee on Animal Research of the Second Affiliated Hospital of Harbin Medical University (Ethics No.KY2016-090) and were in compliance with the principles and regulations of laboratory animal care.
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Supplementary Figure 1
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Supplementary Table S1.
Differentially expressed lncRNA identified by ‘edge R’ R package. (XLSX 34 kb)
Supplementary Table S2.
Differentially expressed mRNA identified by ‘edge R’ R package. (XLSX 36 kb)
Supplementary Table S3.
AS associated lncRNA-mRNA pairs based on hypergeometric test. (XLSX 708 kb)
Supplementary Table S4.
GO enrichment analysis for the first near mRNA neighbors of lncRNA MSTRG.5258.4 in ASLMN. (XLS 25 kb)
Supplementary Table S5.
KEGG enrichment analysis for the first near mRNA neighbors of lncRNA MSTRG.5258.4 in ASLMN. (XLS 27 kb)
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Wu, Y., Zhang, F., Li, X. et al. Systematic analysis of lncRNA expression profiles and atherosclerosis-associated lncRNA-mRNA network revealing functional lncRNAs in carotid atherosclerotic rabbit models. Funct Integr Genomics 20, 103–115 (2020). https://doi.org/10.1007/s10142-019-00705-z
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DOI: https://doi.org/10.1007/s10142-019-00705-z