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.

中文翻译：

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敲低TUG 1可通过上调miR-133a抑制缺氧诱导的心肌细胞凋亡。

lncRNA在心脏病中的作用越来越受到关注。牛磺酸上调基因1（TUG 1）在缺氧诱导的心肌细胞损伤中的生物学作用仍不清楚。我们的研究旨在研究TUG 1在缺氧治疗的心肌细胞中的功能及其可能的潜在机制。通过RT-qPCR检查在低氧培养的人AC16心肌细胞中TUG 1和miR-133a的表达水平。通过CCK-8测定法测定了TUG 1和miR-133a在细胞增殖中的作用。通过流式细胞仪和caspase-3 / 7活性测定评估AC16细胞凋亡。通过蛋白质印迹分析评估切割的聚ADP核糖聚合酶（PARP）和切割的caspase-3的表达水平。我们发现，在缺氧条件下，AC16细胞中TUG 1表达升高，而miR-133a表达降低。TUG 1沉默和miR-133a恢复可缓解低氧诱导的增殖减少，并抑制低氧诱导的AC16细胞凋亡，而在TUG 1过表达和miR-133a抑制后观察到相反的作用。我们确定TUG 1充当竞争内源性RNA，以抑制miR-133a表达。从机制上讲，miR-133a在缺氧条件下推翻了AC16细胞中TUG 1过度表达介导的增殖抑制和凋亡促进作用。相反，在低氧培养的AC16细胞中，抑制miR-133a消除了TUG 1敲低介导的增殖能力的增强和凋亡的抑制。总之，通过上调miR-133a表达，TUG 1敲低可缓解低氧诱导的增殖减少，并抑制低氧诱导的AC16细胞凋亡。