Reconstruction of a lncRNA-Associated ceRNA Network in Endothelial Cells under Circumferential Stress

Abstract

Background. Numerous studies have highlighted that long noncoding RNA (lncRNA) can indirectly regulate the expression of mRNAs by binding to microRNA (miRNA). LncRNA-associated ceRNA networks play a vital role in the initiation and progression of several pathological mechanisms. However, the lncRNA-miRNA-mRNA ceRNA network in endothelial cells under cyclic stretch is seldom studied. Methods. The miRNA, mRNA, and lncRNA expression profiles of 6 human umbilical vein endothelial cells (HUVECs) under circumferential stress were obtained by next-generation sequencing (NGS). We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the R software package GDCRNATools. Cytoscape was adopted to construct a lncRNA-miRNA-mRNA ceRNA network. In addition, through GO and KEGG pathway annotations, we analyzed gene functions and their related pathways. We also adopted ELISA and TUNEL to investigate the effect of si-NEAT1 on endothelial inflammation and apoptosis. Results. We recognized a total of 32978 lncRNAs, 1046 miRNAs, and 31958 mRNAs in 6 samples; among them, 155 different expressed lncRNAs, 74 different expressed miRNAs, and 960 different mRNAs were adopted. Based on the established theory, the ceRNA network was composed of 13 lncRNAs, 44 miRNAs, and 115 mRNAs. We constructed and visualized a lncRNA-miRNA-mRNA network, and the top 20 nodes are identified after calculating their degrees. The nodes with most degrees in three kinds of RNAs are hsa-miR-4739, NEAT1, and MAP3K2. Functional analysis showed that different biological processes enriched in biological regulation, response to stimulus and cell communication. Pathway analysis was mainly enriched in longevity regulating, cell cycle, mTOR, and FoxO signaling pathway. Circumferential stress can significantly downregulate NEAT1, and after transducing si-NEAT1 for 24 h, inflammatory cytokine IL-6 and MCP-1 were significantly increased; furthermore, fewer TUNEL-positive cells were found in the si-NEAT1 treated group. Conclusions. The establishing of a ceRNA network can help further understand the mechanism of vein graft failure. Our data demonstrated that NEAT1 may be a core factor among the mechanical stress factors and that cyclic stress can significantly reduce expression of NEAT1, give rise to inflammation in the early stage of endothelial dysfunction, and promote EC apoptosis, which may play an essential role in vein graft failure.

Potential of ATP5MG to Treat Metabolic Syndrome-Associated Cardiovascular Diseases

“…The ceRNA network controls inflammation through tanshinone IIA in atherosclerosis (34), affects metabolic and proinflammatory responses in coronary artery disease (CAD) (35), and regulates inflammation and cell proliferation in remote ischemic preconditioning of myocardial ischemia-reperfusion injury (36). NEAT1formed ceRNA participates in endothelial dysfunction by regulating inflammation in vein graft failure (37). GATA5mediated ceRNA adjusts cardiac conduction block through an inflammatory process (38).…”

Twist2 Reduced NLRP3-Induced Inflammation of Infantile Pneumonia via Regulation of Mitochondrial Permeability Transition by FOXO1

“…FOXO1 gene, a transcription factor, can regulate cellular oxidative stress response, cell proliferation, apoptosis, autophagy, metabolism, immune response, and other physiological functions [22,23]. FOXO1 mainly plays its biological role by transcribing and transmitting various growth factors and cytokine signals [24].…”

Stool microRNA profiles reflect different dietary and gut microbiome patterns in healthy individuals

“…MiR-4739 has been reported as a hub in the regulatory network mediated by the long non-coding RNA NEAT1 . 48 NEAT1 works as an miRNA sponge and represses the proliferation and fibrosis in diabetic nephropathy. 49 Therefore, the action of NEAT1 as a natural downregulator of miR-4739 may be imitated by a VT or VN diet.…”