Downregulation of microRNA-1 attenuates glucose-induced apoptosis by regulating the liver X receptor α in cardiomyocytes

Abstract

Diabetic cardiomyopathy (DCM) is characterized by abnormal myocardial structure or performance. It has been suggested that microRNA‑1 (miR‑1) may be abnormally expressed in the hearts of patients with diabetes. In the present study, the role of miR‑1 in glucose‑induced apoptosis and its underlying mechanism of action was investigated in rat cardiomyocyte H9C2 cells. Cells were transfected with anti‑miR‑1 or miR‑1‑overexpression plasmids and the expression of miR‑1 and liver X receptor α (LXRα) were determined by reverse transcription‑quantitative polymerase chain reaction analysis. The proportion of apoptotic cells was determined using an Annexin‑V‑FITC apoptosis detection kit and the mitochondrial membrane potential (ΔΨ) was measured following staining with rhodamine 123. In addition, the expression of apoptosis‑associated proteins was measured by western blot analysis. The results demonstrated that expression of miR‑1 was significantly increased, whereas the expression of LXRα was significantly decreased in H9C2 cells following treatment with glucose. miR‑1 knockdown significantly inhibited apoptosis, increased the ΔΨ and suppressed the cleavage of poly (adenosine diphosphate‑ribose) polymerase, caspase‑3 and caspase‑9. It also significantly downregulated the expression of Bcl‑2 and upregulated the expression of Bax. In addition, it was demonstrated that miR‑1 regulates LXRα; transfection with anti‑miR‑1 significantly increased the expression of LXRα. Furthermore, treatment of cells with the LXR agonist GW3965 inhibited apoptosis in glucose‑induced anti‑miR‑1 cells. These results suggest a novel function of miR‑1: The regulation of cardiomyocyte apoptosis via LXRα, and provide novel insights into regarding the complex mechanisms involved in DCM.