lncRNA FGD5 antisense RNA 1 upregulates RORA to suppress hypoxic injury of human cardiomyocyte cells by inhibiting oxidative stress and apoptosis via miR-195

Abstract

FGD5 antisense RNA 1 (FGD5-A S1) is a long non-coding RNA in acute myocardial infarction (AMI), which is primarily caused by myocardial ischemia-hypoxia. Retinoid acid receptor-related orphan receptor α (RORA ) is a key protector in maintaining heart function. However, the roles of FGD5-A S1 and RORA in AMI have not previously been elucidated. The present study investigated the effect and mechanism of FGD5-A S1 and RORA in human cardiomyocyte AC 16 cells under hypoxia. Reverse transcription-quantitative PCR and western blotting demonstrated that FGD5-A S1 and RORA were downregulated in the serum of patients with AMI and hypoxia-challenged AC 16 cells. Functional experiments were performed via assays, flow cytometry and western blotting. In response to hypoxia, superoxide dismutase (SOD ) activity was inhibited, but apoptosis rate and levels of reactive oxygen species and malondialdehyde were promoted in AC 16 cells, accompanied by increased Bax and cleaved caspase-3 expression levels, and decreased SOD 2 and glutathione peroxidase 1 expression levels. However, hypoxia-induced oxidative stress and apoptosis in AC 16 cells were attenuated by ectopic expression of FGD5-A S1 or RORA . Moreover, silencing RORA counteracted the suppressive role of FGD5-A S1 overexpression in hypoxic injury. FGD5-A S1 controlled RORA expression levels via microRNA- 195-5p (miR- 195), as confirmed by dual-luciferase reporter and RNA pull-down assays. Consistently, miR- 195 knockdown suppressed hypoxia-induced oxidative stress and apoptosis in AC 16 cells, which was abrogated by downregulating FGD5-A S1 or RORA . In conclusion, FGD5-A S1 modulated hypoxic injury in human cardiomyocytes partially via the miR- 195/RORA axis, suggesting FGD5-A S1 as a potential target in interfering with the progression of AMI.