Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease

Abstract

Background. Accumulating evidence supports the importance of noncoding RNAs and exosomes in coronary heart disease (CHD). However, exosomal-associated competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms in CHD are largely unexplored. The present study aimed to explore exosomal-associated ceRNA networks in CHD. Methods. Data from 6 CHD patients and 32 normal controls were downloaded from the ExoRBase database. CHD and normal controls were compared by screening differentially expressed mRNAs (DEMs), lncRNAs (DELs), and circRNAs (DECs) in serum exosomes. MicroRNAs (miRNAs) targeting DEMs were predicted using the Targetscan and miRanda databases, and miRNAs targeted by DELs and DECs were predicted using the miRcode and starBase databases, respectively. The biological functions and related signaling pathways of DEMs were analyzed using the David and KOBAS databases. Subsequently, a protein-protein interaction (PPI) network was established to screen out on which hub genes enrichment analyses should be performed, and a ceRNA network (lncRNA/circRNA-miRNA-mRNA) was constructed to elucidate ceRNA axes in CHD. Results. A total of 312 DEMs, 43 DELs, and 85 DECs were identified between CHD patients and normal controls. Functional enrichment analysis showed that DEMs were significantly enriched in “chromatin silencing at rDNA,” “telomere organization,” and “negative regulation of gene expression, epigenetic.” PPI network analysis showed that 25 hub DEMs were closely related to CHD, of which ubiquitin C (UBC) was the most important. Hub genes were mainly enriched in “cellular protein metabolic process” functions. The exosomal-associated ceRNA regulatory network incorporated 48 DEMs, 73 predicted miRNAs, 10 DELs, and 15 DECs. The LncRNA/circRNA-miRNA-mRNA interaction axes (RPL7AP11/hsa-miR-17-5p/UBC and RPL7AP11/hsa-miR-20b-5p/UBC) were obtained from the network. Conclusions. Our findings provide a novel perspective on the potential role of exosomal-associated ceRNA network regulation of the pathogenesis of CHD.

LINC00926 is involved in hypoxia-induced vascular endothelial cell dysfunction <em>via</em> miR-3194-5p regulating JAK1/STAT3 signaling pathway

“…LncRNAs, miRNAs and mRNAs were involved in constructing miRNA-lncRNA-mRNA interaction network, which function critically in CVD. 19 Lin et al 20 reported that lncRNA THRIL relieved myocardial injury via miRNA-424/TXNIP/p53 aixs in CHD mice. Huang et al 21 confirmed that lnc-SLC15A1-1 upregulated CXCL10 and CXCL8 levels by sponging miRNA in HUVECs.…”

Construction of a circRNA-miRNA-mRNA Regulatory Network for Coronary Artery Disease by Bioinformatics Analysis

“…Miao et al established a triple regulatory network of circRNA-miRNA-mRNA and found circ-YOD1 could be a good marker to predict the onset of CAD [ 39 ]. Mao et al constructed a serum exosome-associated ceRNA network to identify the promising diagnostic and therapeutic targets for CAD [ 40 ]. Ji et al performed RNA sequence analysis of circRNAs in peripheral blood mononuclear cells of patients with CAD and constructed a differentially expressed gene-circRNA-miRNA-mRNA network to identify dysregulated circRNAs involved in the pathogenesis of CAD [ 41 ].…”

Molecular Mechanisms and Functions of lncRNAs in the Inflammatory Reaction of Diabetes Mellitus

“…A review has shown that [ 122 ] lncRNAs can regulate gene expression at the transcriptional, posttranscriptional, and epigenetic levels, thereby affecting the clinical course of the disease. Some studies have also demonstrated the key role of lncRNAs in disease development, and their role in heart development and heart disease is particularly prominent [ 123 , 124 ]. Until today, there have been no reviews on the underlying mechanism exploring the role of lncRNAs in diabetes inflammation.…”