Inhibition of long non-coding RNA TUG1 protects against diabetic cardiomyopathy induced diastolic dysfunction by regulating miR-499-5p.

Reportedly, several long non-coding RNAs (lncRNAs) have been involved in the regulation of cardiac hypertrophy induced by diabetic cardiomyopathy (DCM), causing cardiac dysfunction and subsequent failure. Although lncRNA taurine upregulated gene 1 (TUG1) is associated with myocardial injury, the expression profile and potential role of TUG1 in DCM-related cardiac hypertrophy remain unknown. This study elucidated the functions of TUG1 in DCM and its underlying mechanisms. Our results demonstrated that the expression of TUG1 was upregulated in db/db mice cardiomyocytes. Inhibition of TUG1 by lentivirus si-TUG1 indicated no effect on systolic function; however, it effectively improved DCM-induced diastolic dysfunction in db/db mice. TUG1 silencing demonstrated no influence on the metabolic characteristics of DCM, including blood glucose and lipid levels. Notably, TUG1 knockdown significantly decreased cardiac hypertrophy and reduced the fibrotic area, . To further investigate the underlying mechanism, miR-499-5p was predicted as the targeted TUG1 microRNA. The RT-qPCR and luciferase activity results confirmed that TUG1 negatively regulated miR-499-5p in cardiomyocytes. Furthermore, the overexpression of miR-499-5p abated the inhibitory effects of TUG1 silencing on high glucose-mediated cardiac hypertrophy, . Collectively, our study suggested that TUG1 knockdown attenuated DCM-induced cardiac hypertrophy and diastolic dysfunction by upregulating miR-499-5p. lncRNA TUG1 may be a novel potential target for DCM therapy.