LncRNA-GAS5 regulates PDCD4 expression and mediates myocardial infarction-induced cardiomyocytes apoptosis via targeting MiR-21

摘要

The present study was designed to investigate whether and how lncRNA-GAS5 regulates cardiomyocyte apoptosis in MI. MI rat model was established by the left anterior descending (LAD) coronary artery ligation. MI model was further evaluated by biomarkers detection and TUNEL, HE and Masson staining. The roles of lncRNA-GAS5 on hypoxia/reoxygenation (H/R)-induced cardiomyocytes survival, cell cycle arrest, and apoptosis were examined by MTT and flow cytometry in rat heart-derived H9c2 cells. Western blot was used to determine the effect of GAS5 on the expression of apoptosis-associated proteins and PI3 K/AKT signaling pathway. The direct bindings of GAS5 to miR-21 and miR-21 to PDCD4 were measured by dual-luciferase reporter assay or RNA immunoprecipitation. Decreased expressions of GAS5 and PDCD4 as well as increased miR-21 level were observed in the hearts of MI-modeled rat, accompanying with morphologically myocardial cell injury, as well as collagen deposition and fibrosis, and elevated levels of cTnl, CK, CK-MB and LDH. In the cell model, the knockdown of GAS5 promoted cell survival, prevented cell cycle arrest and inhibited cell apoptosis while the overexpression of GAS5 showed the opposite effects. GAS5 was found to downregulate miR-21 and the effects of GAS5 were attenuated by miR-21 mimics. GAS5 positively regulated PDCD4 expression by functioning as a sponge of miR-21 in H/R model. Moreover, GAS5 stimulated PDCD4 and suppressed PI3 K/AKT signal pathway. LncRNA-GAS5 regulates PDCD4 expression to mediate MI-induced cardiomyocyte apoptosis via targeting miR-21, suggesting that GAS5 could be a therapeutic target for MI.