HOTAIR regulates SIRT3-mediated cardiomyocyte survival after myocardial ischemia/reperfusion by interacting with FUS

Abstract

Background Myocardial ischemia/reperfusion (I/R) contributes to serious myocardial injury and even death. Therefore, prevention and mitigation of myocardial I/R is particularly important. LncRNA HOTAIR has been reported to be implicated in myocardial I/R progression. However, the detailed molecular mechanism of HOTAIR in cardiomyocyte was explored in myocardial I/R. Methods Firstly, cell model of myocardial I/R was established through hypoxia/reoxygenation (H/R). Apoptosis and cell cycle were evaluated utilizing flow cytometry. The corresponding test kits were conducted to monitor the levels of LDH, Caspase3 and Caspase9. The gene expression and protein levels were detected by qPCR and western blot, respectively. RNA pull-down and RIP were performed to verify the interaction between FUS and lncRNA HOTAIR. Results In AC16 cardiomyocytes treated with H/R, lncRNA HOTAIR and SIRT3 expression were obviously decreased. Overexpression of HOTAIR or SIRT3 could ameliorate H/R-induced cardiomyocyte injury by promoting cell viability, lowering LDH levels, and suppressing cell apoptosis. Further, lncRNA HOTAIR upregulated the expression of SIRT3 via interacting with FUS, thereby promoting the survival of H/R-injured cardiomyocytes. Conclusion LncRNA HOTAIR can improve myocardial I/R by affecting cardiomyocyte survival through regulation of SIRT3 by binding to the RNA binding protein FUS.

Gasdermin D-Mediated Pyroptosis in Diabetic Cardiomyopathy: Molecular Mechanisms and Pharmacological Implications

“…The latest research has indicated that the overexpression of lncRNA-HOTAIR inhibits the HG-induced GSDMD-mediated pyroptosis and inflammatory response in diabetic cardiomyocytes through the FUS/SIRT3 axis [103]. In addition, cardiomyocyte damage caused by hypoxia/reoxygenation (H/R) can be alleviated by the overexpression of HOTAIR or SIRT3, thereby promoting cell viability and decreasing LDH levels [104]. All the above studies suggest that lncRNA plays a crucial role in cardiovascular disease by regulating the FUS/SIRT3 axis.…”