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, in vivo. 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, in vitro. 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. AJTR