LncRNA NORAD promotes the progression of myocardial infarction by targeting miR-22-3p/PTEN axis

Increasing evidences have demonstrated that lncRNAs are closely associated with the progression of acute myocardial infarction (AMI). Although lncRNA NORAD has been reported to be highly expressed in MI patients, its specific function remains unclear. Here, we found that downregulation of NORAD efficiently attenuated heart damage in an AMI rat model. Meanwhile, silencing of NORAD also inhibited hypoxia/re-oxygenation (H/R)-treated mouse cardiomyocyte cell line HL-1 cells. Further, bioinformatics analysis revealed that NORAD might act as a ceRNA of miR-22-3p, and PTEN was a potential target of miR-22-3p. Then luciferase reporter assay was performed to confirm that NORAD could upregulate PTEN by directly sponging miR-22-3p. Meanwhile, miR-22-3p inhibitor significantly reversed si-NORAD induced inhibitory effect on the apoptosis of H/R-treated HL-1 cells, and overexpression of PTEN could obviously reverse miR-22-3p mimics induced inhibitory effect on the apoptosis of H/R-treated HL-1 cells. Meanwhile, miR-22-3p mimics significantly reversed OE-NORAD (overexpression of NORAD) induced expression of p-AKT and p-mTOR. In a word, our results suggested lncRNA NORAD might promote the progression of myocardial infarction by promoting PTEN/AKT/mTOR signaling pathway through directly sponging miR-22-3p, suggesting that NORAD might be a potential target for AMI treatment.