Abstract
Atherosclerosis is a chronic inflammatory disease with high prevalence and mortality. The rupture of atherosclerotic plaque is the main reason for the clinical events caused by atherosclerosis. Making clear the transcriptomic and proteomic profiles between the stabe and unstable atherosclerotic plaques is crucial to prevent the clinical manifestations. In the present study, 5 stable and 5 unstable human carotid atherosclerotic plaques were obtained by carotid endarterectomy. The samples were used for the whole transcriptome sequencing (RNA-Seq) by the Next-Generation Sequencing using the Illumina HiSeq, and for proteome analysis by HPLC-MS/MS. The lncRNA-targeted genes and circRNA-originated genes were identified by analyzing their location and sequence. Gene Ontology and KEGG enrichment was carried out to analyze the functions of differentially expressed RNAs and proteins. The protein-protein interactions (PPI) network was constructed by the online tool STRING. The consistency of transcriptome and proteome were analyzed, and the lncRNA/circRNA-miRNA-mRNA interactions were predicted. As a result, 202 mRNAs, 488 lncRNAs, 91 circRNAs, and 293 proteins were identified to be differentially expressed between stable and unstable atherosclerotic plaques. The 488 lncRNAs might target 381 protein-coding genes by cis-acting mechanisms. Sequence analysis indicated the 91 differentially expressed circRNAs were originated from 97 protein-coding genes. These differentially expressed RNAs and proteins were mainly enriched in the terms of the cellular response to stress or stimulus, the regulation of gene transcription, the immune response, the nervous system functions, the hematologic activities, and the endocrine system. These results were consistent with the previous reported data in the dataset GSE41571. Further analysis identified CD5L, S100A12, CKB (target gene of lncRNA MSTRG.11455.17), CEMIP (target gene of lncRNA MSTRG.12845), and SH3GLB1 (originated gene of hsacirc_000411) to be critical genes in regulating the stability of atherosclerotic plaques. Our results provided a comprehensive transcriptomic and proteomic knowledge on the stability of atherosclerotic plaques.
Highlights
Atherosclerosis is a chronic inflammatory disease with high prevalence and mortality
To predict the functions or mechanisms of circRNAs, we identified the circRNA-originated genes based on the theory that many circRNAs are originated from protein-coding genes and contain exonic sequences (Guo et al, 2014; You et al, 2015)
Sequence analysis indicated the 91 circRNAs were originated from 97 protein-coding genes
Summary
Atherosclerosis is a chronic inflammatory disease with high prevalence and mortality. LncRNA FENDRR, LincRNA-p21, ANRIL, MIAT, CDK2B-AS1, PELATON participated in the formation and stability of atherosclerotic plaques. They interfered with the phagocytosis, lipid uptake, and reactive oxygen species formation during atherogenesis (Çekin et al, 2018; Hung et al, 2020; Ou et al, 2020). CircRNA is a plentiful, stable, diversified, and conserved class of non-coding RNA molecules that circularized from head to tail with a covalent bond of 5–3 (Jeck et al, 2013) It is involved in a wide range of biological and pathological processes, such as carcinogenesis and cardiovascular diseases. Studies reported the participation of cirRNA00044073, circRNA-PTPRA, circRNA_0003204, and circHIPK3 in atherosclerosis through affecting the autophagy, proliferation and invasion, and tube formation (Shen et al, 2019; Wei et al, 2020; Zhang, 2020; Zhang et al, 2020)
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