Inhibition of long noncoding RNA BLACAT1 protects anesthesia-induced neural cytotoxicity in human induced pluripotent stem cells derived neurons

Abstract

Strong evidence has shown that long non-coding RNAs (lncRNAs) play important roles in genetic modulations in human CNS. In this study, we utilized an in vitro model of human induced pluripotent stem cells (hiPSCs)-derived neurons, and hypothesized that lncRNA of bladder cancer associated transcript 1 (BLACAT1) had a functional role in anesthesia-induced cytotoxicity in human lineage neural cells. To test that, HiPSCs were induced toward neural cells and then treated with ketamine in vitro. We demonstrated that, ketamine induced neuronal apoptosis, neurite degeneration, and upregulated BLACAT1 gene expression. Inversely, lentiviral-induced BLACAT1 downregulation rescued ketamine-induced neural cytotoxicity in hiPSCs-derived neurons. In addition, BLACAT1 downregulation was demonstrated to prevent ketamine-induced mitochondrial dysregulations by suppressing ROS and caspase 3/7 activities in hiPSCs-derived neurons. Thus, we discovered a new mechanism that inhibition of LncRNA BLACAT1 could rescue anesthesia-induced neural cytotoxicity in human induced pluripotent stem cells derived neurons.