Knockdown of TUG 1 suppresses hypoxia-induced apoptosis of cardiomyocytes by up-regulating miR-133a

Abstract

The roles of lncRNAs in cardiac diseases have received increasing attention. The biological role of taurine up-regulated gene 1 (TUG 1) in hypoxia-induced damage of cardiomyocytes is still poorly defined. Our study aimed to investigate the function of TUG 1 in hypoxia-treated cardiomyocytes and the possible underlying mechanism. TUG 1 and miR-133a expression levels in hypoxia-cultured human AC16 cardiomyocytes were examined by RT-qPCR. The role of TUG 1 and miR-133a in cell proliferation was assayed by CCK-8 assay. AC16 cell apoptosis was assessed by flow cytometry and caspase-3/7 activity assay. The expression levels of cleaved poly ADP ribose polymerase (PARP) and cleaved caspase-3 were evaluated by Western blot analysis. We found that TUG 1 expression was elevated, while miR-133a expression was reduced under hypoxic condition in AC16 cells. TUG 1 silencing and miR-133a restoration relieved hypoxia-induced reduction of proliferation as well as repressed hypoxia-induced AC16 cell apoptosis, while the opposite effects were observed after TUG 1 overexpression and miR-133a inhibition. We identified that TUG 1 acted as a competing endogenous RNA to suppress miR-133a expression. Mechanistically, miR-133a overturned TUG 1 overexpression-mediated inhibition of proliferation and promotion on apoptosis in AC16 cells under hypoxic condition. Conversely, inhibition of miR-133a abolished TUG 1 knockdown-mediated promotion of proliferative ability and repression of apoptosis in hypoxia-cultured AC16 cells. In conclusion, TUG 1 knockdown relieved hypoxia-induced reduction of proliferation and repressed hypoxia-induced AC16 cell apoptosis by up-regulating miR-133a expression.

Keywords: Congenital heart disease; Hypoxia; TUG 1; miR-133a.