Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieAtherosclerosis
CeRNA1ZEB1-AS1[LncRNA]
miRNAmiR-590-5p[miRNA]
CeRNA2ETS1[mRNA]
Tissue/Cell lineumbilical vein endothelial cells
SpecieHomo sapiens (human)
CitationJ Cardiovasc Pharmacol. 2021 Apr 1;77(4):480-490. doi: 10.1097/FJC.0000000000000974.
Reference title
Exosomes-Mediated LncRNA ZEB1-AS1 Facilitates Cell Injuries by miR-590-5p/ETS1 Axis Through the TGF-β/Smad Pathway in Oxidized Low-density Lipoprotein-induced Human Umbilical Vein Endothelial Cells.
Experimental verification
ELISA;MTT assay;Western blot;Flow Cytometry assay;MTT assay;
Functional description
Atherosclerosis is a chronic lipid-induced inflammation of the vessel wall. Oxidized low-density lipoprotein was confirmed to drive the onset of atherogenesis. Zinc finger e-box-binding homeobox 1 antisense 1 (ZEB1-AS1) is a long noncoding RNA that is involved in human diseases, including atherosclerosis. In this study, the role of exosomes-mediated ZEB1-AS1 and its underlying mechanisms in atherosclerosis were explored in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). Exosomes were extracted from HUVECs. Quantitative real-time polymerase chain reaction was conducted to measure the expression of ZEB1-AS1, microRNA-590-5p (miR-590-5p), or erythroblastosis virus E26 oncogene homolog 1 (ETS1) in cells or exosomes. Cell proliferation and apoptosis were assessed by MTT assay and flow cytometry analysis, respectively. Western blot was performed to detect apoptosis-related factors, ETS1, and TGF-β/Smad pathway protein levels. The secretion of inflammatory factors in supernatant was detected by ELISA assay. Oxidative stress damage indicators were used to assess cellular damage. Relationship between miR-590-5p and ZEB1-AS1 or ETS1 was analyzed. Our data indicated that ox-LDL-induced exosomes-mediated ZEB1-AS1 in HUVECs. Ox-LDL treatment resulted in limited proliferation, proapoptosis, inflammation, and oxidative stress damage, whereas knockdown of ZEB1-AS1 could reverse these effects. Mechanically, ZEB1-AS1 sponged miR-590-5p to regulate ETS1 expression. MiR-590-5p knockdown inverted effects above of si-ZEB1-AS1 on HUVECs under ox-LDL exposure. Moreover, ETS1 reversed miR-590-5p-induced effects and activated the TGF-β/Smad pathway in ox-LDL-treated HUVECs. Taken together, our findings demonstrated that exosomes-mediated ZEB1-AS1 enhanced cell injuries by miR-590-5p/ETS1 axis through the TGF-β/Smad pathway in ox-LDL-induced HUVECs, suggesting that inhibiting ZEB1-AS1 might be an effective way for atherosclerosis treatment.
Annotations
External Annotation for ZEB1-AS1 |
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LncRNA-associated competing triplets and functions. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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Infer genomic variations that disturb lncRNA-associated ceRNA regulation.. |
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Provide and annotate disease or phenotype-associated variants in human long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) or their regulatory elements. |
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Providing cellular-specific lncRNA-associated ceRNA networks predicted via high-throughput analysis of single-cell genomic data. |
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Information on all annotated and predicted human genes. |
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Gene nomenclature, gene families and associated resources (genomic, proteomic, phenotypic information). |
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Genome browser for vertebrate genomes. |
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An annotated collection of all publicly available DNA sequences. |
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A wiki-based platform for community curation of human long non-coding RNAs. |
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An integrated knowledge database dedicated to non-coding RNAs. |
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An integrated database of human annotated lncRNA transcripts. |
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Comprehensive annotations of eukaryotic long non-coding RNAs. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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A comprehensive, authoritative compendium of human genes and genetic phenotypes. |
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The catalogue of somatic mutations in cancer. |
