基因敲除
炎症
转染
小RNA
神经突
细胞凋亡
癌症研究
下调和上调
细胞生物学
化学
生物
细胞培养
免疫学
基因
体外
生物化学
遗传学
作者
Yuanlong Li,Xiong Han,Hua Fan,Jun Sun,Ming Ni,Lulu Zhang,Fengqin Fang,Wei Zhang,Peizhi Ma
标识
DOI:10.1016/j.neulet.2022.136531
摘要
Our previous study observed that circular RNA AXL (circ-AXL, access number circ_0002945) was closely correlated with disease risk and severity of Alzheimer's Disease (AD) by microarray and RT-qPCR validation. Then this current study aimed to further investigate the effect of circ-AXL on regulating neuron injury and inflammation in cellular AD models and its underlying molecular mechanism.SK-N-SH and SK-SY5Y cell lines were treated by amyloid β to construct cellular AD models. Then control or circ-AXL overexpression, control or circ-AXL knock-down, microRNA-328 (miR-328) knock-down with or without circ-AXL knock-down, as well as BACE1 overexpression with or without miR-328 overexpression plasmids were transfected into cellular AD models. Furthermore, neuron injury and inflammation were detected.Circ-AXL overexpression increased apoptosis rate and declined neurite outgrowth, as well as elevated inflammatory cytokines in cellular AD models; but circ-AXL knockdown exhibited opposite effects. Additionally, circ-AXL negatively regulated miR-328 but positively modulated BACE1; besides, miR-328 negatively regulated BACE1; further luciferase reporter gene assay presented that circ-AXL directly bound miR-328, and miR-328 directly bound BACE1. Furthermore, miR-328 overexpression decreased apoptosis rate, elevated neurite outgrowth, and declined inflammatory cytokines in cellular AD models; but miR-328 knockdown presented opposite effects. Notably, miR-328 knockdown attenuated the effect of circ-AXL knockdown on cellular AD models. Moreover, BACE1 overexpression aggravated neuron injury and inflammation, as well as attenuated the effect of miR-328 overexpression on these functions in cellular AD models.Circ-AXL may serve as a potential treatment target via miR-328 mediated BACE1 in AD.
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