miR-762 modulates thyroxine-induced cardiomyocyte hypertrophy by inhibiting Beclin-1

Whether autophagy plays a key role in thyroxine-induced cardiomyocyte hypertrophy, and whether the role of autophagy in thyroxine-induced cardiomyocyte hypertrophy is related to targeting of Beclin-1 by miR-762 remains unclear. This research focused on testing these two hypotheses. Importantly, the results of this study will help us better understand the molecular mechanisms of thyroxine-induced cardiomyocyte hypertrophy. In vivo and in vitro, RT-PCR, western blot, and dual luciferase reporter assay were performed to understand the molecular mechanism of thyroxine-induced cardiomyocyte hypertrophy. HE staining, Masson staining, transmission electron microscopy, and immunofluorescence were used to observe intuitively changes of hearts and cardiomyocytes. Our results showed that in vivo, serum TT3, TT4, and heart rate were significantly upregulated in the T4 group compared with the control group. Moreover, the surface area of cardiomyocytes was significantly increased in the T4 group, and the structural disorder was accompanied by obvious hyperplasia of collagen fibers. The expression of ANP, and β-MHC was significantly upregulated in the T4 group. In addition, LC3 II/LC3 I, Beclin-1 and the count of autophagic vacuoles were significantly upregulated, but miR-762 was significantly downregulated in the T4 group compared to the control group. Subsequently, a dual luciferase reporter assay suggested that Beclin-1 was the target gene of miR-762. In vitro, the results for the T3 group were consistent with the results for the T4 group. Furthermore, cardiomyocyte hypertrophy and autophagic activity were attenuated in the T3 + miR-762 mimic group compared with the T3 group. In contrast, cardiomyocyte hypertrophy and autophagic activity were aggravated in the T3 + miR-762 inhibitor group compared with the T3 group. miR-762 modulates thyroxine-induced cardiomyocyte hypertrophy by inhibiting Beclin-1.