Dataset Information

Prediction of Functional Genes in Primary Varicose Great Saphenous Veins Using the lncRNA-miRNA-mRNA Network.

ABSTRACT:

Background

Long noncoding RNAs (lncRNAs) have been widely suggested to bind with the microRNA (miRNA) sites and play roles of competing endogenous RNAs (ceRNAs), which can thus affect and regulate target gene and mRNA expression. Such lncRNA-related ceRNAs are identified to exert vital parts in vascular disease. Nonetheless, it remains unknown about how the lncRNA-miRNA-mRNA network functions in the varicose great saphenous veins.

Methods

This study acquired the lncRNA and mRNA expression patterns from the GEO database and identifies the differentially expressed mRNAs and lncRNAs by adopting the R software "limma" package. Then, miRcode, miRDB, miRTarbase, and TargetScan were used to establish the miRNA-mRNA pairs and lncRNA-miRNA pairs. In addition, the lncRNA-miRNA-mRNA ceRNA network was constructed by using Cytoscape. Protein-protein interaction, Gene Ontology functional annotations, and Kyoto Encyclopedia of Genes and Genomes enrichment were carried out to examine the candidate hub genes, the functions of genes, and the corresponding pathways.

Results

In line with the preset theory, we constructed ceRNA network comprising 12 lncRNAs, 38 miRNAs, and 149 mRNAs. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the PI3K/Akt signaling pathway played a vital part in the development of varicose great saphenous veins. AC114730, AC002127, and AC073342 were significant biomarkers. At the same time, we predicted the potential miRNA, which may exert a significant influence on the varicose great saphenous veins, namely, miR-17-5p, miR-129-5p, miR-1297, miR-20b-5p, and miR-33a-3p.

Conclusion

By performing ceRNA network analysis, our study detects new lncRNAs, miRNAs, and mRNAs, which can be applied as underlying biomarkers of varicose great saphenous veins and as therapeutic targets for the treatment of varicose great saphenous veins.

SUBMITTER: Wei J

PROVIDER: S-EPMC9477642 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prediction of Functional Genes in Primary Varicose Great Saphenous Veins Using the lncRNA-miRNA-mRNA Network.

Wei Jiabo J Zhu Haihong H Zhang Qijun Q Zhang Qin Q

Computational and mathematical methods in medicine 20220908

<h4>Background</h4>Long noncoding RNAs (lncRNAs) have been widely suggested to bind with the microRNA (miRNA) sites and play roles of competing endogenous RNAs (ceRNAs), which can thus affect and regulate target gene and mRNA expression. Such lncRNA-related ceRNAs are identified to exert vital parts in vascular disease. Nonetheless, it remains unknown about how the lncRNA-miRNA-mRNA network functions in the varicose great saphenous veins.<h4>Methods</h4>This study acquired the lncRNA and mRNA ex ...[more]

PMID: 36118829

Similar Datasets

Project description:BackgroundThe great saphenous vein (GSV) is the most commonly used conduit for coronary arterial bypass graft. However, the status of the GSV, including metabolic dysfunction such as diabetes mellitus (DM) complication, is strongly associated with vein graft failure (VGF). To date, the molecular mechanism underlying VGF remains elusive. Detailed characterization of the cellular components and corresponding expression regulation in GSVs would be of great importance for clinical decision making to reduce VGF.MethodsTo this end, we performed single-cell RNA sequencing to delineate cellular heterogeneity in three human GSV samples.ResultsScrutinization of cellular composition and expression revealed cell diversity in human GSVs, particularly endothelial cells (ECs). Our results unraveled that functional adaptation drove great expression differences between venous ECs and valvular ECs. For instance, cell surface receptor ACKR1 demarcated venous Ecs, whereas ACRK3/ACKR4 were exclusively expressed by valvular ECs. Differential gene expression analysis suggested that genes highly expressed in venous ECs were mainly involved in vasculature development and regulation of leukocyte adhesion, whereas valvular ECs have more pronounced expression of genes participating in extracellular matrix organization, ossification and platelet degranulation. Of note, pseudo-time trajectory analysis provided in silico evidence indicating that venous ECs, valvular ECs and lymphatic vessels were developmentally connected. Further, valvular ECs might be an importance source for lymphatic vessel differentiation in adults. Additionally, we found a venous EC subset highly expressing IL6, which might be associated with undesirable prognosis. Meanwhile, we identified a population of ANGPTL7+ fibroblasts (FBs), which may be profibrotic and involved in insulin resistance in human GSVs. Additionally, our data suggest that immune cells only accounted for a small fraction, most of which were macrophages. By assessing the intertwined remodeling in metabolic dysfunction that potentially increases the gene expression regulatory network in mural cells and leukocytes, we found that transcription factor KLF9 likely operated a proinflammatory program, inducing the transcription of metallothionein proteins in two mural cell subsets and proinflammatory immune cells. Lastly, cellular communication analysis revealed that proinflammatory signaling, including TRAIL, PVR, CSF and GDF, were uniquely activated in patients with metabolic dysfunction.ConclusionsOur results identified critical cell-specific responses and cellular interactions in GSVs. Beyond serving as a repertoire, this work illustrates multifactorial likelihood of VGF.

Project description:Three-dimensional computed tomography venography is a useful tool to identify increased saphenous vein diameter and provides a complementary road map for surgery in patients with varicose veins. In this study, we investigated the correlation between saphenous vein diameter on computed tomography venography and venous reflux detected on duplex ultraonography. We enrolled 152 patients (213 extremities) who underwent endovenous laser ablation therapy, following high ligation of the saphenofemoral junction between January 2014 and December 2019. All patients underwent preoperative computed tomography venography evaluation. The saphenous vein diameter was measured on computed tomography venography, and venous reflux was evaluated in the operating room using Doppler ultrasonography. Among the 152 patients included in the study, 61 showed varicose veins affecting the bilateral extremities. Among the 213 extremities investigated, 165 (77.5%) and 48 (22.5%) extremities showed varicosities involving the greater and lesser saphenous veins, respectively. Among all extremities, venous reflux was detected in 172 (80.8%). The mean diameter of the greater saphenous vein measured 5 cm distal to the saphenofemoral junction was 8.07±1.82 mm in patients with reflux and 5.11±1.20 mm in patients without reflux (p < .05). The small saphenous vein diameter measured 5 cm distal to the saphenopopliteal junction was 7.65±1.74 mm in patients with reflux and 5.04±1.80 mm in patients without reflux (p < .05). Based on the receiver operating characteristic curve, the greater saphenous vein threshold diameter of 5.880 mm measured 5 cm distal to the saphenofemoral junction was the optimal cut-off value to predict reflux (sensitivity 91.4%, specificity 81.8%). The lesser saphenous vein diameter of 5.285 mm measured 5 cm distal to the saphenopopliteal junction was the optimal cut-off value to predict reflux (sensitivity 94.9%, specificity 75.0%). Vein diameter cannot be used as an absolute reference for venous reflux; however, it may have predictive value in patients with varicose veins. Computed tomography venography based measurements of vein diameter may serve as a useful diagnostic tool to predict venous reflux and recommend treatment.

Project description:Long non-coding RNAs (lncRNAs) are ncRNA transcripts >200 nucleotides that are important genetic regulators. LncRNAs can directly regulate mRNA through a lncRNA-mRNA regulatory mode and can also regulate mRNA through competitive binding to micro (mi)RNA, which is generally known as the competitive endogenous RNA (ceRNA) network. The present study evaluated the functional roles and regulatory networks of lncRNAs in chronic glomerulonephritis (CGN). The proliferative ability of mouse glomerular mesangial cells (GMCs) induced by different concentrations of lipopolysaccharide (LPS) was assessed using the Cell Counting Kit-8 assay, and RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs in LPS-induced GMCs. Based on the sequencing results, six lncRNAs were selected for validation using reverse transcription-quantitative PCR (RT-qPCR). Furthermore, the lncRNA-mRNA regulatory network and the lncRNA-miRNA-mRNA ceRNA network were constructed to assess the role and mechanism of CGN-related lncRNAs. To elucidate the biological functions of lncRNAs, Gene Ontology (GO) biological process term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on all mRNAs involved in the lncRNA-mRNA regulatory network and in the ceRNA network. A total of 1,532 differentially expressed lncRNAs, including 594 upregulated lncRNAs and 938 downregulated lncRNAs, were identified using RNA-seq. The results of RT-qPCR validation were consistent with RNA-seq results. An lncRNA-mRNA regulatory network, including 236 lncRNAs and 556 mRNAs, and a ceRNA network, including 6 lncRNAs, 18 miRNAs and 419 mRNAs, were successfully constructed. The GO biological process term enrichment and KEGG pathway enrichment analyses demonstrated that those lncRNAs were often related to inflammatory response and substance metabolism. The present study identified key CGN-related lncRNAs in LPS-induced GMCs, and further demonstrated a global view of the lncRNA-mRNA regulatory network and ceRNA network involved in CGN. These results offered novel insights into the roles of lncRNAs in the pathogenesis of CGN and identified potential diagnostic biomarkers.

Dataset Information

Prediction of Functional Genes in Primary Varicose Great Saphenous Veins Using the lncRNA-miRNA-mRNA Network.

Background

Methods

Results

Conclusion

Publications

Prediction of Functional Genes in Primary Varicose Great Saphenous Veins Using the lncRNA-miRNA-mRNA Network.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets