机构:[1]Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, P. R. China[2]Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, P. R. China[3]Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, P. R. China[4]Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, P. R. China临床科室心脏内科中心首都医科大学附属安贞医院
Doxorubicin (DOX) is an effective anticancer drug, however its clinical application is limited due to its cardiotoxicity. Therefore, understanding the mechanisms of cardiotoxicity induced by DOX is essential. We found that the level of miR-378 was decreased in the hearts of DOX-treated rats. Increasingthe expression of miR-378 resulted in a decrease of lactate dehydrogenase (LDH) upon DOX treatment in vitro by targeting lactate dehydrogenase A (LDHA). Furthermore, bioinformatics analysis indicated that cyclophilin A (PPIA), a regulator of apoptosis, is also a direct target gene of miR-378. We confirmed this by Western blot. Our results also showed that the overexpression of miR-378 inhibited the hyperactivation of ER stress signaling induced by DOX. In addition, MiR-378 overexpression was found to protect cardiomyocytes from DOX-induced energy imbalance and apoptosis of mitochondria. These results may allow for a therapeutic approach that overcomes the cardiotoxicity of DOX-based treatments for cancer.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81360587, 81760780]; natural science foundation of Inner Mongolia [2016BS0806]; higher scientific research project of Inner Mongolia [NJZY17195]; graduate research and innovation project of Inner Mongolia University for Nationalities [NMDSS1754]
第一作者机构:[1]Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, P. R. China[3]Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, P. R. China
共同第一作者:
通讯作者:
通讯机构:[1]Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, P. R. China[2]Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, P. R. China[3]Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, P. R. China[*1]Affiliated Hospital of Inner Mongolia University for Nationalities, No. 1472 Holin He Street, Tongliao 028002, Inner Mongolia, P. R. China.
推荐引用方式(GB/T 7714):
Wang Yu,Zhang Qingshan,Wei Chengxi,et al.MiR-378 modulates energy imbalance and apoptosis of mitochondria induced by doxorubicin[J].AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH.2018,10(11):3600-3609.
APA:
Wang, Yu,Zhang, Qingshan,Wei, Chengxi,Zhao, Lin,Guo, Xin...&Zhao, Ming.(2018).MiR-378 modulates energy imbalance and apoptosis of mitochondria induced by doxorubicin.AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH,10,(11)
MLA:
Wang, Yu,et al."MiR-378 modulates energy imbalance and apoptosis of mitochondria induced by doxorubicin".AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH 10..11(2018):3600-3609