lncRNA Oip5-as1 attenuates myocardial ischaemia/reperfusion injury by sponging miR-29a to activate the SIRT1/AMPK/PGC1α pathway.
Cell Prolif
; 53(6): e12818, 2020 Jun.
Article
em En
| MEDLINE
| ID: mdl-32468629
ABSTRACT
OBJECTIVES:
Myocardial ischaemia/reperfusion (MI/R) injury is associated with adverse cardiovascular outcomes after acute myocardial infarction. However, the molecular mechanisms underlying MI/R injury are unclear. This study investigated the role of long non-coding RNA (lncRNA) Oip5-as1 in regulating mitochondria-mediated apoptosis during MI/R injury. MATERIALS ANDMETHODS:
Sprague-Dawley rats were subjected to MI/R induced by ligation of the left anterior descending coronary artery followed by reperfusion. H9c2 cells were incubated under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to mimic in vivo MI/R. RT-qPCR and Western blot were used to evaluate gene and protein levels. CCK-8 assay, biochemical assay and flow cytometric analysis were performed to assess the function of Oip5-as1. The dual-luciferase gene reporter assay and RIP assay were conducted as needed.RESULTS:
Oip5-as1 expression was downregulated in the hearts of rats with MI/R and in H9c2 cells treated with OGD/R. Oip5-as1 overexpression alleviated reactive oxygen species-driven mitochondrial injury and consequently decreased apoptosis in MI/R rats and H9c2 cells exposed to OGD/R. Mechanistically, Oip5-as1 acted as a competing endogenous RNA of miR-29a and thus decreased its expression. Inhibition of miR-29a reduced the oxidative stress and cytotoxicity induced by OGD/R. Overexpression of miR-29a reversed the anti-apoptotic effect of Oip5-as1 in H9c2 cells treated with OGD/R. Further experiments identified SIRT1 as a downstream target of miR-29a. Oip5-as1 upregulated SIRT1 expression and activated the AMPK/PGC1α pathway by targeting miR-29a, thus reducing the apoptosis triggered by OGD/R. However, these effects were reversed by a selective SIRT1 inhibitor, EX527.CONCLUSIONS:
Oip5-as1 suppresses miR-29a leading to activation of the SIRT1/AMPK/PGC1α pathway, which attenuates mitochondria-mediated apoptosis during MI/R injury. Our findings thus provide new insights into the molecular mechanisms of MI/R injury.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão Miocárdica
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MicroRNAs
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Proteínas Quinases Ativadas por AMP
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Sirtuína 1
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RNA Longo não Codificante
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Prolif
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China