Let-7 g is involved in doxorubicin induced myocardial injury.
OBJECTIVE
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 μmol/l, 0.004 μmol/l, 0.02 μmol/l, 0.1 μmol/l, 0.5 μmol/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.
Department of Toxicology, Health Science Center, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, PR China.
Jun
J
Fu
Cike
C
Peng
Wanyi
W
Wang
Haifeng
H
Jin
Qiuqiong
Q
Tang
Xuetao
X
Wei
D000818:Animals; D000903:Antibiotics, Antineoplastic; D001794:Blood Pressure; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D004317:Doxorubicin; D006331:Heart Diseases / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D020107:Troponin T / Q000097:blood
D000903:Antibiotics, Antineoplastic; C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; D020107:Troponin T; D004317:Doxorubicin