Suppression of LncRNA-ATB Prevents Amyloid-β-induced Neurotoxicity in PC12 Cells Via Regulating MiR-200/ZNF217 Axis

Objective: 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.

Material And Methods: 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 Aβ to induce cell injury. The lncRNA-ATB expression in Aβ-treated PC12 cells was also determined. Moreover, the effects of lncRNA-ATB suppression on Aβ-induced PC12 cell injury were investigated by assessing cell viability, apoptosis, cytotoxicity, and oxidative stress (intracellular Ca 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.

Results: The results showed that lncRNA-ATB was increased expressed in the CSF and serum of patients with AD. Aβ-induced injury in PC12 cells and increased the expression of lncRNA-ATB. Suppression of lncRNA-ATB alleviated Aβ-induced PC12 cell injury. Further studies showed that miR-200 was negatively regulated by lncRNA-ATB. Suppression of lncRNA-ATB alleviated Aβ injury by regulation of miR-200. Moreover, miR-200 negatively regulated ZNF217 expression and ZNF217 was a target of miR-200.

Conclusions: Our findings indicate that lncRNA-ATB is highly expressed in AD patients. Suppression of lncRNA-ATB may protect PC12 cells against Aβ-induced neurotoxicity via regulating miR-200/ZNF217 axis. LncRNA-ATB/miR-200/ZNF217 axis may provide a new insight for preventing AD.