ATG5型
基因敲除
自噬
免疫印迹
流式细胞术
细胞凋亡
下调和上调
分子生物学
生物
化学
细胞生物学
癌症研究
生物化学
基因
作者
Yuan Zhou,Yao Ge,Qi Liu,Yunxiao Li,Xu Chen,Jianjun Guan,Yong-Chang Diwu,Qi Zhang
出处
期刊:Neuroscience
[Elsevier]
日期:2021-02-01
卷期号:455: 52-64
被引量:40
标识
DOI:10.1016/j.neuroscience.2020.10.028
摘要
Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by progressive memory loss and cognitive dysfunction. Long non-coding RNAs (lncRNAs) have been shown to be among the most promising biomarkers and therapeutic targets of AD. Here, we aimed to investigate whether lncRNA BACE1-AS plays a role in the potential mechanisms of AD. The expression of BACE1-AS, miR-214-3p and ATG5 mRNA was detected using qRT-PCR. The expression of the LC3, P62, ATG5, Bcl-2, p-Tau and cleaved-caspase 3 proteins was examined using western blot analysis. Cell apoptosis, cytotoxicity and ROS levels were estimated using flow cytometry, an LDH kit and a DCFH-DA assay, respectively. The interaction between BACE1-AS or ATG5 and miR-214-3p was validated using a dual-luciferase reporter assay. HE staining and a TUNEL assay were employed to evaluate hippocampal neuronal injury. The BACE1-AS level was found to be upregulated in serum samples of AD patients, brain tissues of AD transgenic (Tg) mice and Aβ1-42-treated SH-SY5Y cells. Autophagy activity was increased in both Tg mice and Aβ1-42-treated cells. BACE1-AS knockdown alleviated Aβ1-42-induced cell injury. Rapamycin abolished the protective effects of sh BACE1-AS against Aβ1-42 induced cell injury. BACE1-AS indirectly regulated ATG5 expression by binding miR-214-3p. The miR-214-3p inhibitor reversed the protective effects of sh BACE1-AS and sh ATG5 against Aβ1-42-induced cell injury. Knockdown of BACE1-AS alleviated neuronal injury by repressing autophagy in vivo. Our findings demonstrate that silencing of BACE1-AS alleviated neuronal injury by regulating autophagy through the miR-214-3p/ATG5 signalling axis in AD.
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