High expression of microRNA-208 is associated with cardiac hypertrophy via the negative regulation of the sex-determining region Y-box 6 protein

Abstract

The aim of this study was to investigate the expression levels of microRNA-208 (miR-208) and sex-determining region Y-box 6 (SOX6) in patients with progressive cardiac hypertrophy. A total of 50 patients with essential hypertension accompanied by left ventricular hypertrophy, and 30 healthy individuals were enrolled. Peripheral blood samples were collected in order to compare miR-208 expression levels between the cardiac hypertrophy patients and healthy individuals. In addition, an in vitro cellular model of cardiac hypertrophy was established to determine the association between miR-208 and SOX6 expression. Rat cardiomyocytes were treated with phenylephrine (PE) to induce cardiac hypertrophy. Some of the hypertrophic cardiomyocytes were subsequently transfected with antagomiR-208, an miR-208 antagonist, in order to determine the effects of silencing miR-208 expression. Differences between healthy and hypertrophic cardiomyocyte morphology were evaluated using immunofluorescence staining. The mRNA expression levels of the hypertrophy-associated genes ß-myosin heavy chain, a-sarcomeric actin and atrial natriuretic peptide were determined using quantitative polymerase chain reaction (qPCR). The mRNA and protein expression levels of miR-208 and SOX6 in peripheral blood and cardiomyocytes were detected using qPCR and western blot analysis, respectively. The expression levels of miR-208 were significantly increased in the peripheral blood of patients with left ventricular hypertrophy (P<0.05). PE-stimulated cardiomyocytes were significantly increased in size compared with normal cardiomyocytes. In the PE-stimulated cardiomyocytes, miR-208 expression levels were significantly increased (P<0.05). However, SOX6 expression levels were significantly decreased compared with those in normal cardiomyocytes (P<0.05). Following transfection with antagomiR-208, SOX6 expression levels in the PE-stimulated cardiomyocytes significantly increased, while the total mRNA and protein expression levels of hypertrophy-associated genes significantly decreased (P<0.05). miR-208 expression levels are increased in the peripheral blood of patients with cardiac hypertrophy. Therefore, the results of this study suggest that the expression levels of miR-208 are associated with cardiac hypertrophy by the negative regulation of SOX6.