Functional lncRNA-miRNA-mRNA networks in rabbit carotid atherosclerosis

Abstract

Atherosclerosis is one of the most common clinical cardiovascular disorders. Accumulating evidence indicates that lncRNAs exert critical functions in atherosclerosis; however, their functional roles and regulatory mechanisms remain unclear. In this study, we induced atherosclerotic plaques in three rabbit carotid arteries through an atherogenic diet and balloon injury; three age-matched rabbits were fed normal chow and served as controls. We thoroughly investigated the RNA (mRNA, lncRNA and miRNA) expression profiles in atherosclerotic rabbit carotid models with deep RNA sequencing. We identified several significantly differentially expressed RNAs. The corresponding lncRNA-miRNA-mRNA network was constructed, and the significantly dysregulated network was selected. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that the mRNAs in the network were involved in leukocyte activation, cell proliferation, cell adhesion molecules and cytokine-cytokine receptor interaction. After rigorous screening, we obtained a differentially expressed lncRNA-miRNA-mRNA interaction network associated with atherosclerosis. In the network, <i>XLOC_054118</i> and <i>XLOC_030217</i> upregulate the <i>CHI3L1</i>, <i>SOAT</i>, <i>CTSB</i> and <i>CAPG</i> genes by competitively binding to the miRNA <i>ocu-miR-96-5p</i>. <i>XLOC_062719</i> and <i>XLOC_063297</i> upregulate <i>CTSS</i>, <i>CTSB</i> and <i>EDNRA</i> genes by competitively binding to the miRNA <i>ocu-miR-185-5p</i>.