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TRA2A-induced upregulation of LINC00662 regulates blood-brain barrier permeability by affecting ELK4 mRNA stability in Alzheimer's microenvironment.
RNA Biology ( IF 4.1 ) Pub Date : 2020-05-06 , DOI: 10.1080/15476286.2020.1756055
Qianshuo Liu 1, 2, 3 , Lu Zhu 1, 2, 3 , Xiaobai Liu 4, 5, 6 , Jian Zheng 4, 5, 6 , Yunhui Liu 4, 5, 6 , Xuelei Ruan 1, 2, 3 , Shuo Cao 1, 2, 3 , Heng Cai 4, 5, 6 , Zhen Li 4, 5, 6 , Yixue Xue 1, 2, 3
Affiliation  

The blood-brain barrier (BBB) plays a pivotal role in the maintenance and regulation of the neural microenvironment. The BBB breakdown is a pathological change in early Alzheimer’s disease (AD). RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) are involved in the regulation of BBB permeability. Our study demonstrates the role of TRA2A/LINC00662/ELK4 axis in regulating BBB permeability in AD microenvironment. In Aβ1-42-incubated microvascular endothelial cells (ECs) of the BBB model in vitro, TRA2A and LINC00662 were enriched. TRA2A increased the stability of LINC00662 by binding with it. The knockdown of either TRA2A or LINC00662 decreased BBB permeability due to increased expression of tight junction-related proteins. ELK4 was less expressed in the BBB model in AD microenvironment in vitro. LINC00662 mediated the degradation of ELK4 mRNA by SMD pathway. Downregulation of ELK4 increased BBB permeability by increasing the tight junction-related protein expression.TRA2A/LINC00662/ELK4 axis plays a crucial role in the regulation of BBB permeability in AD microenvironment, which may provide a novel target for the therapy of AD.



中文翻译:

TRA2A诱导的LINC00662上调通过影响阿尔茨海默氏症微环境中的ELK4 mRNA稳定性来调节血脑屏障通透性。

血脑屏障(BBB)在维持和调节神经微环境中起着关键作用。BBB分解是早期阿尔茨海默氏病(AD)的病理变化。RNA结合蛋白(RBPs)和长非编码RNA(lncRNAs)参与BBB通透性的调节。我们的研究证明了TRA2A / LINC00662 / ELK4轴在AD微环境中调节BBB渗透性中的作用。在Aβ1-42中培养的BBB模型体外微血管内皮细胞(EC),TRA2A和LINC00662被富集。TRA2A通过与LINC00662结合而提高了稳定性。TRA2A或LINC00662的敲低会降低BBB的通透性,原因是紧密连接相关蛋白的表达增加。在体外AD微环境中, ELB4在BBB模型中表达较少。LINC00662通过SMD途径介导了ELK4 mRNA的降解。ELK4的下调通过增加紧密连接相关蛋白的表达而增加了BBB的通透性。TRA2A/ LINC00662 / ELK4轴在AD微环境中对BBB通透性的调节中起着至关重要的作用,这可能为AD治疗提供新的靶点。

更新日期:2020-05-06
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