Let-7 g is involved in doxorubicin induced myocardial injury.

Abstract

OBJECTIVES: To investigate whether let-7 g (miRNA) was involved in doxorubicin-induced cardiotoxicity. METHODS: Rats were treated with doxorubicin at increasing doses (0mg/kg, 6 mg/kg, 12 mg/kg, 18 mg/kg). Heart rate, pulse pressure and plasma cardiac troponin T concentrations were measured. Primary cultured myocardial cells were incubated with DOX at increasing concentrations (0 &#x3bc;mol/l, 0.004 &#x3bc;mol/l, 0.02 &#x3bc;mol/l, 0.1 &#x3bc;mol/l, 0.5 &#x3bc;mol/l) for 24h. Cellular viability and the beat frequency were measured. For both rats and cultured cells, miRNA content was measured by real-time reverse-transcription PCR. RESULTS: All DOX-treated rats had a decrease in heart rate, an increase in pulse pressure compared with control group after injections (p<0.05). Concentration of cTnT was increased significantly in 18 mg/kg group. Content of let-7 g decreased significantly (p<0.05) in 18 mg/kg group in vivo and all the doxorubicin treated group in vitro. CONCLUSIONS: The down regulation of let-7 g in the myocardial-injury model suggests that let-7 g may play an important role in the development of cardiac disease.