Silencing of lncRNA ZFAS1 protects against hypoxia/reoxygenation-induced injury in HL-1 cells through targeting the miR-761/CDIP1 axis.

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) have demonstrated to be associated with AMI pathogenesis. In this study, we aimed to investigate the function and mechanism of zinc finger antisense 1 (ZFAS1) on hypoxia/reoxygenation (H/R)-induced injury in HL-1 cells. The levels of ZFAS1, miR-761 and cell death inducing p53 target 1 (CDIP1) in the serum of AMI patients and HL-1 cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability and apoptosis were assessed by the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Lactate dehydrogenase (LDH) release, malondialdehyde (MDA) content, superoxide dismutase (SOD) expression and glutathione peroxidase (GSH-PX) were evaluated using commercially corresponding assay kits. Targeted interactions among ZFAS1, miR-761 and CDIP1 were validated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Our data indicated that ZFAS1 was up-regulated and miR-761 was down-regulated in the serum of AMI patients and H/R-induced HL-1 cells. ZFAS1 silencing or miR-761 overexpression alleviated H/R-induced injury in HL-1 cells. Moreover, ZFAS1 acted as a sponge to sequester miR-761 and CDIP1 was directly targeted and inhibited by miR-761. ZFAS1 knockdown protected HL-1 cell from H/R-induced injury via miR-761, and CDIP1 mediated the alleviated effect of miR-761 overexpression on H/R-induced HL-1 cell injury. Furthermore, ZFAS1 regulated CDIP1 expression through acting as a miR-761 sponge. Additionally, CDIP1 silencing protected HL-1 cell from H/R-induced injury. Our current work suggested that the knockdown of ZFAS1 protected against H/R-induced injury in HL-1 cells at least partly through the regulation of miR-761/CDIP1 axis, illuminating a novel therapeutic avenue for AMI management.