Systematic analysis of lncRNA expression profiles and atherosclerosis-associated lncRNA-mRNA network revealing functional lncRNAs in carotid atherosclerotic rabbit models Original Article First Online: 07 August 2019 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. Keywords LncRNA, Atherosclerosis, RNA-seq, Network analysis, Carotid atherosclerotic rabbit models Electronic supplementary material
The online version of this article (
) contains supplementary material, which is available to authorized users. https://doi.org/10.1007/s10142-019-00705-z Notes Funding information
Present research was supported by the National Natural Science Foundation of China (No. 81671689) and the Natural Science Foundation of Heilongjiang Province (H2017021).
Compliance with ethical standards
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.
Conflict of interest
The authors declare that they have no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary material 10142_2019_705_MOESM9_ESM.xls (26 kb) Supplementary Table S4. GO enrichment analysis for the first near mRNA neighbors of lncRNA MSTRG.5258.4 in ASLMN. (XLS 25 kb) 10142_2019_705_MOESM10_ESM.xls (27 kb) Supplementary Table S5. KEGG enrichment analysis for the first near mRNA neighbors of lncRNA MSTRG.5258.4 in ASLMN. (XLS 27 kb) References
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