LncRNA TUG1 mediates ischemic myocardial injury by targeting miR-132-3p/HDAC3 axis

作者：Qiang Su, Yang Liu, Xiangwei Lv, Rixin Dai, Xiheng Yang, Binghui Kong · 发表于：American Journal of Physiology-Heart and Circulatory Physiology · 年份：2019 · DOI：10.1152/ajpheart.00444.2019 · 被引用次数：100 · 研究领域：Cancer-related molecular mechanisms research、Circular RNAs in diseases、MicroRNA in disease regulation

Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). In this study, we explored the functional significance and molecular mechanisms of TUG1/miR-132-3p axis in ischemia-challenged cardiomyocytes. In primary cardiomyocytes challenged with H 2 O 2 , expressions of miR-132-3p, TUG1, and other target proteins were measured by RT quantitative PCR or Western blot analysis; cell viability by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay; apoptosis by annexin V and propidium iodide staining; the abundance of acetylated H3K9 or histone deacetylase 3 (HDAC3) within the promoter of target genes by chromatin immunoprecipitation; the direct interaction between miR-132-3p and HDAC3 or TUG1 by luciferase reporter assay. The biological significance of miR-132-3p, TUG1, and HDAC3 was assessed using miR-132-3p mimic, siRNA-targeting TUG1 and HDAC3 inhibitor RGF966, respectively, in H 2 O 2 -challenged cells in vitro or ischemia-reperfusion (I/R)-induced AMI in vivo. miR-132-3p was downregulated, whereas TUG1 upregulated in H 2 O 2 -challenged cardiomyocytes. Overexpressing miR-132-3p or knocking down TUG1 significantly improved viability, inhibited apoptosis, and reduced ROS production in H 2 O 2 -stressed cardiomyocytes in vitro and alleviated I/R-induced AMI in vivo. Mechanistically, ...