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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.

A large number of long non-coding RNAs have been confirmed to play vital roles in regulating various biological processes. Abnormal expression of growth arrest-specific transcript 5 (GAS5) is reported to be involved in the development of atherosclerosis (AS). This work is to explore the detailed mechanism underling how GAS5 regulates AS progression. We found that the abundance of GAS5 was markedly increased, and miR-135a was decreased in AS patient serums and ox-LDL-induced human THP-1 cells dose and time dependently. Interference of GAS5 suppressed inflammation and oxidative stress induced by ox-LDL in THP-1 cells. Mechanistically, GAS5 acted as a molecular sponge of microRNA-135a (miR-135a). Rescue assays indicated that knockdown of miR-135a partially rescued small interference RNA for GAS5-inhibited inflammatory cytokines release and oxidative stress in ox-LDL-triggered THP-1 cells. In conclusion, the absence of GAS5-inhibited inflammatory response and oxidative stress induced by ox-LDL in THP-1 cells via sponging miR-135a, providing a deep insight into the molecular target for AS treatment.

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.