Let-7g is involved in doxorubicin induced myocardial injury

ObjectivesTo investigate whether let-7g (miRNA) was involved in doxorubicin-induced cardiotoxicity.MethodsRats were treated with doxorubicin at increasing doses (0 mg/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 μmol/l, 0.004 μmol/l, 0.02 μmol/l, 0.1 μmol/l, 0.5 μmol/l) for 24 h. Cellular viability and the beat frequency were measured. For both rats and cultured cells, miRNA content was measured by real-time reverse-transcription PCR.ResultsAll 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-7g decreased significantly (p < 0.05) in 18 mg/kg group in vivo and all the doxorubicin treated group in vitro.ConclusionsThe down regulation of let-7g in the myocardial-injury model suggests that let-7g may play an important role in the development of cardiac disease.

► We build up cardiac injury models with doxorubicin both in vivo and in vitro.
► Cardiac injury indicators were examined in the model.
► We examine the quantity of miRNA (let-7g) in the models.
► Content of let-7g decreased significantly (p < 0.05) after doxorubicin treatment in 18 mg/kg group in vivo and all the doxorubicin treated group in vitro.
► Decreasing quantity of let-7g in the models suggests that let-7g may play an important role in the development of cardiac disease.