Construction of lncRNA-related ceRNA regulatory network in diabetic subdermal endothelial cells

Abstract

Long non-coding RNAs (lncRNAs) were considered to be involved in vascular complications in diabetes mellitus, but still only limited knowledge in this regard has been obtained. Herein, we further explored the roles of lncRNAs and mRNAs in diabetic vasculopathy (DV) through conducting bioinformatics analysis using data set downloaded from GEO database. The differentially expressed lncRNAs and mRNAs were identified by edge package. GO enrichment analysis and KEGG pathway analysis were performed based on clusterprofiler package. The relationship between lncRNA and miRNA was predicted using starBase database, and the potential mRNAs targeted by miRNAs were predicted by TargetScan, miRTarbase and miRDB database. The string database was used to analyze the protein-protein interaction (PPI). As a result, a total of 12 lncRNAs and 711 mRNAs were found to be differentially expressed in the diabetic subdermal endothelial cells compared with normal controls. A ceRNA network was established, which was composed of seven lncRNA nodes, 49 miRNA nodes, 58 mRNA nodes and 183 edges, and MSC-AS1 and LINC01550 may serve as key nodes. GO function enrichment analysis showed enrichments of epithelial cell proliferation, intercellular junction, and cell adhesion molecule binding. KEGG pathway analysis revealed 33 enriched pathways. PPI protein interaction analysis identified 57 potential ceRNA-related proteins. Overall, this study suggests that multiple lncRNAs, specifically MSC-AS1 and LINC01550, may play an important role in DV development and they are like to be developed as the therapeutic targets for DV. However, further experiments in vitro and in vivo should be conducted to validate our results.

lncRNA MSC-AS1 Aggravates Diabetic Nephropathy by Regulating the miR-325/CCNG1 Axis

“…Besides, it has been reported that lncRNA MSC-AS1 promoted cell proliferation and migration in renal clear cell carcinoma through miR-3924/WNT5A [ 9 ]. Wan et al found that lncRNA MSC-AS1 may play an important role in the development of diabetic vasculopathy (DV) and is expected to become a therapeutic target for DV [ 17 ]. These studies indicate that the lncRNA MSC-AS1 may be involved in diabetic and kidney-associated diseases.…”

LINC00467 Is Upregulated by DNA Copy Number Amplification and Hypomethylation and Shows ceRNA Potential in Lung Adenocarcinoma

“…The down-stream mechanisms of lncRNAs have also been widely investigated in cancer ( 7 ). ceRNAs are a common molecular regulatory mechanism of lncRNAs, and they have been intensively reported in different cancer types ( 6 , 34 , 35 ). According to the ceRNA hypothesis, lncRNAs can form a sponge with miRNAs to regulate the expression of target genes at the mRNA level ( 6 ).…”

Long non-coding RNA MEG3 inhibits neovascularization in diabetic retinopathy by regulating microRNA miR-6720-5p and cytochrome B5 reductase 2

“…The lncRNA-miRNA-mRNA network has been extensively studied as biomarker and potential therapeutic target for disease diagnosis and prognosis [ 38 ]. For example, Wan et al [ 39 ] established multiple ceRNA networks in patients with diabetic vascular complications. Tong et al [ 40 ] revealed that MEG3 inhibited the NF-κB signaling pathway by targeting the miR-34a/SIRT1 axis; thus reducing HG-induced cell apoptosis and inflammatory responses.…”