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

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.