BACKGROUND/AIMS: Acute myocardial infarction is a serious disease with high morbidity and mortality. microRNAs (miRNAs) have been proved to play an important role in modulating myocardial ischemia and reperfusion injury. Hence, in this study, we constructed H9c2 cell model to elucidate the roles of microRNA-486 (miR-486) in preventing hypoxia-induced damage in H9c2 cells. METHODS: H9c2 cells were cultured in hypoxic incubator with 1% O2 to simulate hypoxia and/or transfected with miR-486 mimic, scramble, anti-miR-486, si-N-myc downstream-regulated gene 2 (NDRG2) and their corresponding negative controls (NC). Effects of miR-486 and/or NDRG2 dysregulation on hypoxia-induced myocardial injury in H9c2 cells were investigated by evaluating cell viability, migration, invasion and apoptosis using Cell Counting Kit-8 (CCK-8), transwell assay, flow cytometry, respectively. The proteins expression and RNA expression were detected by western blot and quantitative real time polymerase chain reaction (qRT-PCR), respectively. RESULTS: Hypoxia treatment induced damage in H9c2 cells by decreasing cell viability, migration and invasion and increasing cell apoptosis. Moreover, hypoxia inhibited the expression of miR-486 in H9c2 cells. Overexpression of miR-486 alleviated hypoxia-induced myocardial injury in H9c2 cells, while suppression of miR-486 further aggravated hypoxia-induced injury. Furthermore, NDRG2 expression was negatively regulated by miR-486, and NDRG2 was confirmed as a target of miR-486. Knockdown of NDRG2 alleviated the effects of miR-486 suppression on hypoxia-induced myocardial injury. Besides, knockdown of NDRG2 markedly inhibited the activation of c-Jun N-terminal kinase (JNK) /c-jun and nuclear factor κB (NF-κB) signaling pathways in hypoxia-induced H9c2 cells. CONCLUSION: Our findings indicate that miR-486 may alleviate hypoxia-induced myocardial injury possibly by targeting NDRG2 to inactivate JNK/c-jun and NF-κB signaling pathways. miR-486 may be a potential target for treating ischemic myocardial injury following acute myocardial infarction.
BACKGROUND/AIMS: Acute myocardial infarction is a serious disease with high morbidity and mortality. microRNAs (miRNAs) have been proved to play an important role in modulating myocardial ischemia and reperfusion injury. Hence, in this study, we constructed H9c2 cell model to elucidate the roles of microRNA-486 (miR-486) in preventing hypoxia-induced damage in H9c2 cells. METHODS: H9c2 cells were cultured in hypoxic incubator with 1% O2 to simulate hypoxia and/or transfected with miR-486 mimic, scramble, anti-miR-486, si-N-myc downstream-regulated gene 2 (NDRG2) and their corresponding negative controls (NC). Effects of miR-486 and/or NDRG2 dysregulation on hypoxia-induced myocardial injury in H9c2 cells were investigated by evaluating cell viability, migration, invasion and apoptosis using Cell Counting Kit-8 (CCK-8), transwell assay, flow cytometry, respectively. The proteins expression and RNA expression were detected by western blot and quantitative real time polymerase chain reaction (qRT-PCR), respectively. RESULTS: Hypoxia treatment induced damage in H9c2 cells by decreasing cell viability, migration and invasion and increasing cell apoptosis. Moreover, hypoxia inhibited the expression of miR-486 in H9c2 cells. Overexpression of miR-486 alleviated hypoxia-induced myocardial injury in H9c2 cells, while suppression of miR-486 further aggravated hypoxia-induced injury. Furthermore, NDRG2 expression was negatively regulated by miR-486, and NDRG2 was confirmed as a target of miR-486. Knockdown of NDRG2 alleviated the effects of miR-486 suppression on hypoxia-induced myocardial injury. Besides, knockdown of NDRG2 markedly inhibited the activation of c-Jun N-terminal kinase (JNK) /c-jun and nuclear factor κB (NF-κB) signaling pathways in hypoxia-induced H9c2 cells. CONCLUSION: Our findings indicate that miR-486 may alleviate hypoxia-induced myocardial injury possibly by targeting NDRG2 to inactivate JNK/c-jun and NF-κB signaling pathways. miR-486 may be a potential target for treating ischemic myocardial injury following acute myocardial infarction.