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Background Many studies have elucidated the regulatory roles of long non-coding RNAs in cardiovascular diseases. The current research was conducted to investigate the involvement of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) with microRNA-135a-5p (miR-135a-5p) and hypoxia-inducible factor 1-alpha subunit inhibitor (HIF1AN) in myocardial ischemia-reperfusion (I/R) injury. Methods A hypoxia-reoxygenation (H/R) model was established in rat cardiomyocytes. RNA or protein level analysis was implemented via qRT-PCR and Western blot. MTT assay was conducted for cell viability detection. H/R injury was evaluated using lactate dehydrogenase assay. The assessment of apoptosis was carried out through flow cytometry and caspase-3 assay. Enzyme-linked immunosorbent assay was applied for determining inflammatory cytokines. Target relation analysis was implemented through dual-luciferase reporter, RNA immunoprecipitation and pull-down assays. MALAT1 function in vivo was evaluated using rat H/R model and infarct areas were determined by triphenyltetrazolium chloride staining. Results MALAT1 and HIF1AN were up-regulated in H/R model of cardiomyocytes. H/R promoted cell apoptosis and inflammatory cytokine release in cardiomyocytes, while these effects were ameliorated by MALAT1 or HIF1AN knockdown. HIF1AN up-regulation reverted the protective function by MALAT1 knockdown in H/R cardiomyocytes. MALAT1 upregulated the HIF1AN expression through absorbing miR-135a-5p. Silencing MALAT1 activated the PI3K/AKT pathway via downregulating HIF1AN. MALAT1 inhibition reduced infarct and apoptosis by depending on the miR-135a-5p/HIF1AN axis in vivo. Conclusion MALAT1 aggravate the H/R-stimulated myocardial I/R injury through the mediation of miR-135a-5p/HIF1AN axis.

Many studies have elucidated the regulatory roles of long non-coding RNAs in cardiovascular diseases. The current research was conducted to investigate the involvement of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) with microRNA-135a-5p (miR-135a-5p) and hypoxia-inducible factor 1-alpha subunit inhibitor (HIF1AN) in myocardial ischemia-reperfusion (I/R) injury.A hypoxia-reoxygenation (H/R) model was established in rat cardiomyocytes. RNA or protein level analysis was implemented via qRT-PCR and Western blot. MTT assay was conducted for cell viability detection. H/R injury was evaluated using lactate dehydrogenase assay. The assessment of apoptosis was carried out through flow cytometry and caspase-3 assay. Enzyme-linked immunosorbent assay was applied for determining inflammatory cytokines. Target relation analysis was implemented through dual-luciferase reporter, RNA immunoprecipitation and pull-down assays. MALAT1 function in vivo was evaluated using rat H/R model and infarct areas were determined by triphenyltetrazolium chloride staining.MALAT1 and HIF1AN were up-regulated in H/R model of cardiomyocytes. H/R promoted cell apoptosis and inflammatory cytokine release in cardiomyocytes, while these effects were ameliorated by MALAT1 or HIF1AN knockdown. HIF1AN up-regulation reverted the protective function by MALAT1 knockdown in H/R cardiomyocytes. MALAT1 upregulated the HIF1AN expression through absorbing miR-135a-5p. Silencing MALAT1 activated the PI3K/AKT pathway via downregulating HIF1AN. MALAT1 inhibition reduced infarct and apoptosis by depending on the miR-135a-5p/HIF1AN axis in vivo.MALAT1 aggravate the H/R-stimulated myocardial I/R injury through the mediation of miR-135a-5p/HIF1AN axis.