Suppression of  lncRNA LINC00472 Prevents Amyloid-β-induced Neurotoxicity in PC12 Cells via Regulating miR-141-3p/Foxo3 Axis 

Abstract Alzheimer's Disease (AD) is characterized by the accumulations of amyloid-β (Aβ) plaques and neurofibrillary tangles in brain, dysfunctions and loss of synaptic connections, exaggerated inflammation, and eventually neuronal death. Oxidative damage may explain the key features and suggest the therapeutic potential to prevent AD progression, yet it remains largely elusive the occurrence and thus the interventions of oxidative damage. Besides, miRNA dysregulation is tightly associated with AD progression. By recruiting 30 AD patients and 30 age-matched control, we demonstrated the upregulations of LINC00472, pro-inflammatory cytokines and ROS in the serum of AD subjects. Similar results were reproduced in Aβ treated SH-SY5Y cells. In addition, through luciferase reporter and RNA pull-down assays, we revealed direct interactions between LINC00472 and miR-141-3p, and between miR-141-3p and FOXO3 and the signalling loop LINC00472/miR-141-3p/FOXO3 loop is involved in Aβ administration induced oxidative stress. Moreover, we raised evidence that knocking down LINC00472 in SH-SY5Y cells ameliorated the Aβ administration induced oxidative stress. Thus, normalization of LINC00472 may be therapeutic to retard AD progression via ameliorating oxidative stress. Future works may further strengthen the pharmacological potentials of interventions for AD progression by targeting LINC00472/ miR-141-3p/ FOXO3 loop.