Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieNeuroblastoma
CeRNA1FOXD3-AS1[LncRNA]
miRNAmiR-765[miRNA]
CeRNA2BCL2L13[mRNA]
Tissue/Cell lineneuroblastoma cells
SpecieHomo sapiens (human)
CitationBiomed Pharmacother. 2020 Dec;132:110778. doi: 10.1016/j.biopha.2020.110778. Epub 2020 Oct 14.
Reference title
LncRNA FOXD3-AS1 knockdown protects against cerebral ischemia/reperfusion injury via miR-765/BCL2L13 axis.
Experimental verification
qRT-PCR;RNA immunoprecipitation;Western blot;Flow Cytometry assay;Luciferase reporter assay;RNA immunoprecipitation;
Functional description
AIMS: Long non-coding RNAs (lncRNAs) FOXD3-AS1 was reported to be increased in cardiomyocyte ischemic injury. However, its role and underlying molecular mechanism in ischemic stroke remain unknown. This study was to investigate the role of FOXD3-AS1 in cerebral ischemia/reperfusion injury. METHODS: The expression of FOXD3-AS1 and miR-765 were measured with qRT-PCR. The shared putative miR-765 binding sites both in BCL2L13 and FOXD3-AS1 were identified with bioinformatics, luciferase reporter assay and RNA immunoprecipitation. Apoptosis and its related proteins were detected by TUNEL assay, Hoechst 33,258 staining, flow cytometry and western blot. Infarct volume and the neurological status were evaluated with TTC staining and neurologic deficit score, respectively. RESULTS: The up-regulation of FOXD3-AS1 and down-regulation of miR-765 were found in both mouse brains after cerebral ischemia/reperfusion (I/R) and neuroblastoma cells of neuro-2A (N2a) after oxygen-glucose deprivation/reoxygenation (OGD/R). Moreover, the overexpression of miR-765 reduced N2a cell apoptosis caused by OGD/R. MiR-765 could target BCL2L13 directly. In addition, we found that FOXD3-AS1 bound to miR-765 directly, acting as a ceRNA to modulate the expression of BCL2L13. Overexpression of FOXD3-AS1 antagonized the inhibitory impact of miR-765 on the expression of BCL2L13 and the apoptosis of N2a cells treated with OGD/R, while FOXD3-AS1 knockdown promoted the inhibitory impact of miR-765 on the expression of BCL2L13 and the apoptosis of N2a cells treated with OGD/R. Furthermore, we found that neurological deficits and brain injury induced by I/R in vivo were attenuated by FOXD3-AS1 knockdown. CONCLUSIONS: We verified a critical signaling pathway of FOXD3-AS1/miR-765/BCL2L13 in regulating cerebral ischemia/reperfusion injury.
Annotations
External Annotation for FOXD3-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. |
