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. 2022 Apr 15:2022:4895611.
doi: 10.1155/2022/4895611. eCollection 2022.

Construction and Analysis of lncRNA-Associated ceRNA Network in Atherosclerotic Plaque Formation

Danyu Li  1 , Yunci Ma  2 , Weiqian Deng  1 , Jianhua Feng  1
Affiliations

Construction and Analysis of lncRNA-Associated ceRNA Network in Atherosclerotic Plaque Formation

Danyu Li et al. Biomed Res Int. .

Abstract

Atherosclerosis (AS) is a vascular disease with plaque formation. Unstable plaques can be expected to result in cardiovascular disease, such as myocardial infarction and stroke. Studies have verified that long noncoding RNAs (lncRNAs) play a critical role in atherosclerotic plaque formation (APF), including MALAT1, GAS5, and H19. A ceRNA network is a combination of these two interacting processes, which regulate the occurrence and progression of many diseases. However, lncRNA-associated ceRNA network in terms of APF is limited. This study sought to discover novel potential biomarkers and ceRNA network for APF. We designed a triple network based on the lncRNA-miRNA and mRNA-miRNA pairs obtained from lncRNASNP and starBase. Differentially expressed genes (DEGs) and lncRNAs in human vascular tissues derived from the Gene Expression Omnibus database (GSE43292, GSE97210) were systematically selected and analyzed. A ceRNA network was constructed by hypergeometric test, including 8 lncRNAs, 243 miRNAs, and 8 mRNAs. APF-related ceRNA structure was discovered for the first time by combining network analysis and statistical validation. Topological analysis determined the key lncRNAs with the highest centroid. GO and KEGG enrichment analysis indicated that the ceRNA network was primarily enriched in "regulation of platelet-derived growth factor receptor signaling pathway," "negative regulation of leukocyte chemotaxis," and "axonal fasciculation." A functional lncRNA, HAND2-AS1, was identified in the ceRNA network, and the main miRNA (miRNA-570-3p) regulated by HAND2-AS1 was further screened. This present study elucidated the important function of lncRNA in the origination and progression of APF and indicated the potential use of these hub nodes as diagnostic biomarkers and therapeutic targets.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Flowchart for an overview of the present analysis.
Figure 2
Figure 2
The global triple ceRNA network. The green nodes represent mRNAs, the red nodes represent lncRNAs, and the blue nodes represent miRNAs.
Figure 3
Figure 3
Identification of differentially expressed genes from the GSE97210 dataset and the GSE43292 dataset. (a) The boxplots of the sample expression level in GSE97210 and GSE43292. (b) The volcano plot of the differential expressed genes between the APF and control group in GSE97210 and GSE43292. (c) Heat map of the expression profiles including DEGs and lncRNAs between the APF and control group in GSE97210 and GSE43292.
Figure 4
Figure 4
Construction of the network related to APF by Cytoscape. The green nodes represent mRNAs, the red nodes represent lncRNAs, and the blue nodes represent miRNAs.
Figure 5
Figure 5
Signaling pathway enrichment analysis for APF-related genes by Cytoscape. (a) A functionally grouped network of enriched categories for target genes. Every node is a disease-related GO term. (b) The proportion of each term.
Figure 6
Figure 6
ceRNA regulatory network of the miRNA bound by HAND2-AS1 and the gene function of the network. (a) The ceRNA network of hsa-miRNA-570-3p sponged by lncRNA HAND2-AS1. (b) Gene function analysis of the ceRNA network.
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