Long Non-coding RNA Taurine Up-regulated Gene 1 Exacerbates Cardiac Fibrosis and Cardiomyocyte Apoptosis After Acute Myocardial Infarction by Modulating the MicroRNA-27a-3p/Zinc-finger Protein 36 Axis

Purpose Increasing data supports the significant involvement of both long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the pathogenesis of acute myocardial infarction (AMI). This study intends to explore the role of lncRNA Taurine up-regulated gene 1 (TUG1) in cardiac fibrosis and cardiomyocyte apoptosis in AMI via modulating the miR-27a-3p/Zinc-finger protein 36 (ZFP36) axis. Methods A myocardial infarction (MI) mouse model was established by ligating the left anterior descending coronary artery. The mice were injected with the vectors correspondingly. Cardiac function, myocardial tissue pathology, cardiomyocyte apoptosis, and cardiac fibrosis were assessed. Mouse cardiomyocyte line HL-1 cells after hypoxia treatment were transfected, and cell proliferation and apoptosis were analyzed. The relationship between TUG1, miR-27a-3p and ZFP36 was tested. Results Levels of TUG1 and ZFP36 were elevated, while the level of miR-27a-3p level was reduced in MI mice and hypoxia-treated HL-1 cells. Myocardial fibrosis and cardiomyocyte apoptosis were alleviated in MI mice after decreasing TUG1 or increasing miR-27a-3p. In cell experiments, knockdown of TUG1 or overexpression of miR-27a-3p reduced cardiomyocyte apoptosis and promoted proliferation. Inhibition of miR-27a-3p attenuated the effects of TUG1 downregulationin vivoandin vitro. TUG1 acted as a sponge for miR-27a-3p, which targeted ZFP36. Up-regulation of ZFP36 counteracted the effects of miR-27a-3p overexpression in hypoxic HL-1 cells. Conclusion TUG1 exacerbates cardiac fibrosis and cardiomyocyte apoptosis after AMI via the miR-27a-3p/ZFP36 axis.