Basic Information
Regular Relationship :
Phenotype/DiseaseSpecie6-Gingerol Relieves Myocardial Ischamia Reperfusion Injury
CeRNA1H19[LncRNA]
miRNAmiR-143[miRNA]
CeRNA2ATG7[mRNA]
Tissue/Cell lineHL-1 cells
SpecieHomo sapiens (human)
CitationLab Invest. 2021 Jul;101(7):865-877. doi: 10.1038/s41374-021-00575-9. Epub 2021 Mar 23.
Reference title
6-Gingerol relieves myocardial ischaemia/reperfusion injury by regulating lncRNA H19/miR-143/ATG7 signaling axis-mediated autophagy.
Experimental verification
Flow cytometry assay;Western blot;Flow Cytometry assay;Immunohistochemistry;
Functional description
Myocardial ischemia/reperfusion injury (MIRI) causes severe damage in cardiac tissue, thereby resulting in a high rate of mortality. 6-Gingerol (6-G) is reported to play an essential role in alleviating MIRI. However, the underlying mechanism remains obscure. This study was intended to explore the potential mechanism by which 6-G functions. Q-PCR was employed to quantify the relative RNA levels of long noncoding RNA (lncRNA) H19 (H19), miR-143, and ATG7, an enzyme essential for autophagy, in HL-1 cells. Western blotting, immunofluorescence, and immunohistochemistry were employed for protein evaluation in cultured cells or mouse tissues. Cell viability, cytotoxicity, and apoptosis were analysed by CCK-8, LDH, and flow cytometry assays, respectively. The binding sites for miR-143 were predicted using starBase software and experimentally validated through a dual-luciferase reporter system. Here, we found that 6-G elevated cellular H19 expression in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Moreover, 6-G increased Bcl-2 expression but reduced cleaved caspase 3 and caspase 9 protein levels. Mechanistically, H19 directly interacted with miR-143 and lowered its cellular abundance by acting as a molecular sponge. Importantly, ATG7 was validated as a regulated gene of miR-143, and the depletion of miR-143 by H19 caused an increased in ATG7 expression, which in turn promoted the autophagy process. Last, mouse experiments highly supported our in vitro findings that 6-G relieves MIRI by enhancing autophagy. The H19/miR-143/ATG7 axis was shown to be critical for the function of 6-G in relieving MIRI.
Annotations
External Annotation for H19 |
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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. |
