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

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.