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MiR-101 Attenuates Myocardial Infarction-induced Injury by Targeting DDIT4 to Regulate Autophagy

[ Vol. 17 , Issue. 2 ]

Author(s):

Qiulan Li, Yanping Gao, Jie Zhu and Qingzhe Jia*   Pages 123 - 130 ( 8 )

Abstract:


Background: Myocardial Infarction (MI), a kind of heart deficiency, is the main cause of death and disability. Autophagy, a metabolic process for the degradation of damaged proteins or organelles, is important for cardiac functions and regulated by several miRNAs including miRNA- 101. The aim of this research was to investigate the effects of miR-101 in myocardial infarctioninduced injury and the related mechanisms.

Methods: MI model was induced by ligation of the left coronary artery. The in vitro model was established by hypoxia-induced H9c2 cells (rat myocardial cells). The overexpression of miR-101 was achieved by transfection. The expression of associated proteins was analyzed by Western blotting. The level of miR-101 was analyzed by reverse transcription-polymerase chain reaction (RTPCR). The target genes for miR-101 and the target sites were analyzed by TargetScan.

Results: The results showed that miR-101 was decreased in MI mice (P<0.01). Autophagy and apoptosis were increased in MI-induced injury (in vivo) and in hypoxia treated myocardial cells (in vitro) (P<0.01). miR-101 overexpression inhibited the increase of autophagy and apoptosis in mice and myocardial cells (P<0.01). DDIT4 was a target gene of miR-101 and expressed increasingly in MI-induced injury mice and hypoxia treated myocardial cells. miR-101 could negatively regulate the expression of DDIT4.

Conclusion: This research suggested that miR-101 attenuated- MI-induced injury by targeting DDIT4 to regulate autophagy, which indicated that miR-101 or DDIT4 may be potential therapeutic targets for heart injury.

Keywords:

miRNA-101, myocardial infarction-induced injury, DNA damage-inducible transcript 4, autophagy, tissue, heart.

Affiliation:

Department of Anesthesiology, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang City, Jiangsu Province, 215600, Department of Anesthesiology, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang City, Jiangsu Province, 215600, Department of Anesthesiology, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang City, Jiangsu Province, 215600, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing City, Jiangsu Province, 210029



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