Suppression of lncRNA-ATB prevents amyloid-β-induced neurotoxicity in PC12 cells via regulating miR-200/ZNF217 axis.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline with loss of memory. The objective of this study was to investigate the role and regulatory mechanism of lncRNA-ATB in regulating amyloid-β-induced neurotoxicity in neuronal PC12 cells. The expression levels of lncRNA-ATB in cerebrospinal fluid (CSF) and serum of patients with Alzheimer's disease (AD) were determined. In addition, PC12 cells were incubated with 20 μM Aβ25-35 to induce cell injury. The lncRNA-ATB expression in Aβ25-35-treated PC12 cells was also determined. Moreover, the effects of lncRNA-ATB suppression on Aβ25-35-induced PC12 cell injury were investigated by assessing cell viability, apoptosis, cytotoxicity, and oxidative stress (intracellular Ca2+ and ROS concentrations and JC-1 mitochondrial membrane potential). Moreover, the regulatory relationships between lncRNA-ATB and miR-200 were explored, as well as the targets of miR-200 were identified. The results showed that lncRNA-ATB was increased expressed in the CSF and serum of patients with AD. Aβ25-35-induced injury in PC12 cells and increased the expression of lncRNA-ATB. Suppression of lncRNA-ATB alleviated Aβ25-35-induced PC12 cell injury. Further studies showed that miR-200 was negatively regulated by lncRNA-ATB. Suppression of lncRNA-ATB alleviated Aβ25-35 injury by regulation of miR-200. Moreover, miR-200 negatively regulated ZNF217 expression and ZNF217 was a target of miR-200. Our findings indicate that lncRNA-ATB is highly expressed in AD patients. Suppression of lncRNA-ATB may protect PC12 cells against Aβ25-35-induced neurotoxicity via regulating miR-200/ZNF217 axis. LncRNA-ATB/miR-200/ZNF217 axis may provide a new insight for preventing AD.