Down-Regulation of Mir-107 Worsen Spatial Memory by Suppressing SYK Expression and Inactivating NF-ΚB Signaling Pathway

锡克 细胞生物学 表达式(计算机科学) NF-κB 信号转导 癌症研究 小RNA 化学 生物 计算机科学 基因 生物化学 程序设计语言 酪氨酸激酶
作者
Wenjie Hu,Lin Wen,Fang Cao,Yexin Wang
出处
期刊:Current Alzheimer Research [Bentham Science Publishers]
卷期号:16 (2): 135-145 被引量:17
标识
DOI:10.2174/1567205016666181212154347
摘要

Alzheimer's Disease (AD) is a chronic progressive neurodegenerative disorder in a central nervous system seen.We aimed to study the miR-107 in Alzheimer's Disease (AD) pathology through regulating SYK and NF-κB signaling pathway.Bioinformatics analysis was performed to screen NF-κB signaling pathway and differentially expressed genes. The target relationship between miR-107 and SYK was verified by dual luciferase assay. QRT-PCR and western blot analysis were used to verify the expression level of miR-107, SYK and NF- κB signaling pathway related proteins of hippocampus primary neurons. BAY61-3606 and BAY11-7082 were purchased for functional examination. Morris water maze tests were performed to access spatial memory of AD mice with SYK and NF-κB signaling pathway inhibition. Fluorescence microscope dyeing experiment investigated the neurons nuclear form and apoptosis.MiR-107 was lowly expressed while SYK was highly expressed in Tg19959 mouse model. Luciferase Assay confirmed the target relationship in miR-107 and SYK. With the inhibition of miR-107, SYK was up-regulated and the increase of p-p65 and the decrease of p-IκB-α suggested that NF-κB signaling pathway was activated in vitro. Morris water maze test indicated that the spatial memory of Tg19959 mice was increased with the treatment. The result of DAPI staining indicated that the inhibition of SYK or NF-κB signaling pathway reduced the apoptosis of Tg19959 mice neuron cell.MiR-107 exerts its effects through suppression of the NF-κB signaling pathway and SYK, the inhibition of SYK and NF-κB signaling pathway can improve spatial memory and suppress cell apoptosis.
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