Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieLymphangiogenesis
CeRNA1GAS5[LncRNA]
miRNAmiR-217[miRNA]
CeRNA2Prox1[mRNA]
Tissue/Cell lineHG-induced lymphatic endothelial cells
SpecieMus musculus (mouse)
CitationMol Cell Endocrinol. 2021 Jul 15;532:111283. doi: 10.1016/j.mce.2021.111283. Epub 2021 Apr 15.
Reference title
Long noncoding RNA GAS5 accelerates diabetic wound healing and promotes lymphangiogenesis via miR-217/Prox1 axis.
Experimental verification
Flow cytometry assay;qRT-PCR;Western blot;Flow Cytometry assay;luciferase assay;
Functional description
BACKGROUND: Diabetes is usually the leading cause of chronic non-healing wounds. LncRNA-GAS5 has been verified to be involved in the regulation of diabetes or high glucose (HG)-stimulated cells. However, its regulatory roles in diabetic wound healing need further investigation. METHOD: GAS5, miR-217 and Prox1 were identified by qRT-PCR. MTT, flow cytometry assay, wound-healing assay and tube formation were used to analyze cell viability, apoptosis, migration and tube formation capacity. Western blotting was carried out to detect the protein expression of c-Myc, CyclinD1, CDK4, Bcl-2, Prox1, VEGFR-3 and LYVE-1. Bioinformatics and luciferase assay were performed to predict and validate the binding sites of miR-217 on GAS5 and Prox1. Immunofluorescence staining detected the expression and distribution of Prox1. The wound healing rate was also assessed by setting up the diabetic mouse model. H&E staining assessed the distribution of inflammatory cells and fibroblasts in the wound tissues. RESULTS: GAS5 was significantly down-regulated whereas miR-217 was obviously up-regulated in diabetic skin, HG-induced lymphatic endothelial cells (LECs) and diabetic mouse model. GAS5 sponged miR-217 to up-regulate Prox1. GAS5 overexpression or miR-217 inhibition rescued the impairments of cell viability, migration and lymphatic vessel formation and the facilitation of apoptosis of LECs caused by HG. Similar impacts were observed on the protein level of VEGFR-3, LYVE-1, and Prox1. GAS5 promoted wound healing and lymphangiogenesis in the diabetic mouse model. CONCLUSION: GAS5 sponged miR-217 to up-regulate Prox1 and promote lymphangiogenesis and diabetic wound healing. This might provide novel therapeutic strategy to improve the efficacy of diabetic wound healing.
Annotations
External Annotation for GAS5 |
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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. |
