Quanbao Wang1, Xiumin Ge2, Jie Zhang3, Licheng Chen1. 1. Department of Neurology, The People’s Hospital of Linyi City, Linyi 276000, P.R. China. 2. Department of Neurology, Linyi Mental Health Center, Linyi 276000, P.R. China. 3. Department of Emergency Internal Medicine, The People’s Hospital of Linyi City, Linyi 276000, P.R. China.
Abstract
OBJECTIVE: To study the effect of lncRNA WT1-AS on oxidative stress injury (OSI) and apoptosis of neurons in Alzheimer's disease (AD) and its specific mechanisms related to the microRNA-375 (miR-375)/SIX4 axis and WT1 expression. RESULTS: After bioinformatic prediction, WT1-AS was found to be downregulated in Aβ25-35treated SH-SY5Y cells, and WT1-AS overexpression inhibited WT1 expression. WT1 could target miR-375 to promote its expression. miR-375 bound to SIX4, and miR-375 overexpression inhibited SIX4 expression. WT1-AS inhibited OSI and apoptosis, while WT1 and miR-375 overexpression or SIX4 silencing reversed the WT1-AS effect on OSI and apoptosis. In vivo experiments revealed that WT1-AS improved learning/memory abilities and inhibited OSI and apoptosis in AD mice. CONCLUSION: Overexpression of WT1-AS can inhibit the miR-375/SIX4 axis, OSI and neuronal apoptosis in AD by inhibiting WT1 expression. METHODS: Related lncRNAs were identified, and miR-375 downstream targets were predicted. WT1-AS, WT1, miR-375 and SIX4 expression was detected in a cell model induced by Aβ25-35. The binding of WT1 with miR-375 and that of miR-375 with SIX4 were further confirmed. Adenosine triphosphate (ATP), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) activities, and apoptosis levels were tested after mitochondrial membrane potential observation. Learning/memory abilities and neuronal apoptosis were tested in a mouse model.
OBJECTIVE: To study the effect of lncRNA WT1-AS on oxidative stress injury (OSI) and apoptosis of neurons in Alzheimer's disease (AD) and its specific mechanisms related to the microRNA-375 (miR-375)/SIX4 axis and WT1expression. RESULTS: After bioinformatic prediction, WT1-AS was found to be downregulated in Aβ25-35treated SH-SY5Y cells, and WT1-AS overexpression inhibited WT1expression. WT1 could target miR-375 to promote its expression. miR-375 bound to SIX4, and miR-375 overexpression inhibited SIX4expression. WT1-AS inhibited OSI and apoptosis, while WT1 and miR-375 overexpression or SIX4 silencing reversed the WT1-AS effect on OSI and apoptosis. In vivo experiments revealed that WT1-AS improved learning/memory abilities and inhibited OSI and apoptosis in ADmice. CONCLUSION: Overexpression of WT1-AS can inhibit the miR-375/SIX4 axis, OSI and neuronal apoptosis in AD by inhibiting WT1expression. METHODS: Related lncRNAs were identified, and miR-375 downstream targets were predicted. WT1-AS, WT1, miR-375 and SIX4expression was detected in a cell model induced by Aβ25-35. The binding of WT1 with miR-375 and that of miR-375 with SIX4 were further confirmed. Adenosine triphosphate (ATP), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) activities, and apoptosis levels were tested after mitochondrial membrane potential observation. Learning/memory abilities and neuronal apoptosis were tested in a mouse model.
Authors: Wen Li; Yu Liu; Zi Jin Li; Yi Shi; Jing Deng; Jie Bai; Liang Ma; Xiao Xi Zeng; Shan Shan Feng; Jia Li Ren; Fei Jun Luo; Duo Yan Rong; Xiao Qi Chen; Hua Qun Yin; Zhu Chen; Fu Da Journal: Biomolecules Date: 2021-02-02
Authors: Estefania Lozano-Velasco; Carlos Garcia-Padilla; Maria Del Mar Muñoz-Gallardo; Francisco Jose Martinez-Amaro; Sheila Caño-Carrillo; Juan Manuel Castillo-Casas; Cristina Sanchez-Fernandez; Amelia E Aranega; Diego Franco Journal: Int J Mol Sci Date: 2022-03-04 Impact factor: 5.923