Ghrelin Relieves Obesity-Induced Myocardial Injury by Regulating the Epigenetic Suppression of <b><i>miR-196b</i></b> Mediated by lncRNA HOTAIR

Abstract

<b><i>Introduction:</i></b> Obesity has been believed to be closely linked with many kinds of diseases including atherosclerosis, hypertension, cerebrovascular thrombosis, and diabetes. Ghrelin and Homeobox transcript antisense RNA (HOTAIR) were believed to be involved in the regulation of myocardial injury. <b><i>Methods:</i></b> The obesity mice model was established through feeding mice (C57BL/6J, male, eight-week-old) with high-fat diet and palmitate (PA)-induced cardiomyocyte injury. RNA and protein levels were detected with Quantitative real-time PCR and Western blotting. The levels of TG, TCH, LDL, CK-MB, cTnl, and BNP in the serum or cell medium supernatant were measured using ELISA kits. The ROS level was detected with the DCFH-DA method. Binding sites between different targets were identified using detection of dual luciferase reporter assay. Cell apoptosis was analyzed by flow cytometry. RNA-binding protein immunoprecipitation and chromatin immunoprecipitation were used to detect the binding of <i>DNMT3B</i> with HOTAIR or <i>miR-196b</i> promoter. <b><i>Results:</i></b> The expression of HOTAIR was downregulated, and <i>miR-196b</i> was upregulated in the obese myocardial injury. Ghrelin attenuated PA-induced cardiomyocyte injury by increasing HOTAIR. HOTAIR regulated the expression of <i>miR-196b</i> by recruiting <i>DNMT3B</i> to induce methylation of the <i>miR-196b</i> gene promoter. The binding site between <i>miR-196b</i> and <i>IGF-1</i> was identified. <b><i>Discussion/Conclusion:</i></b> We demonstrated that ghrelin attenuated PA-induced cardiomyocyte injury by regulating the HOTAIR/<i>miR-196b</i>/<i>IGF-1</i> signaling pathway. Our findings might provide novel thought for the prevention and treatment of obesity-induced myocardial injury by targeting HOTAIR/<i>miR-196b</i>.