101. TRA2A-induced upregulation of LINC00662 regulates blood-brain barrier permeability by affecting ELK4 mRNA stability in Alzheimer’s microenvironment
- Author
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Qianshuo Liu, Yunhui Liu, Heng Cai, Zhen Li, Xiaobai Liu, Shuo Cao, Xuelei Ruan, Jian Zheng, Lu Zhu, and Yixue Xue
- Subjects
RNA Stability ,Biology ,Blood–brain barrier ,Permeability ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Alzheimer Disease ,medicine ,Humans ,ets-Domain Protein Elk-4 ,Promoter Regions, Genetic ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Gene knockdown ,Messenger RNA ,Amyloid beta-Peptides ,Tight Junction Proteins ,Chemistry ,Endothelial Cells ,RNA-Binding Proteins ,Cell Biology ,In vitro ,Peptide Fragments ,Cell biology ,medicine.anatomical_structure ,nervous system ,Cellular Microenvironment ,Gene Expression Regulation ,Permeability (electromagnetism) ,Blood-Brain Barrier ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Molecular targets ,cardiovascular system ,RNA Interference ,RNA, Long Noncoding ,Blood brain barrier permeability ,Bbb permeability ,Biomarkers ,Research Paper ,Protein Binding - Abstract
The blood-brain barrier (BBB) has an important significance in maintenance and regulation of the neural microenvironment. The occurrence of BBB disruption is the pathological change of early Alzheimer’s disease (AD). RNA-binding proteins and long non-coding RNAs are closely related to the regulation of BBB permeability. Our study was performed to demonstrate TRA2A/LINC00662/ELK4 axis that regulates BBB permeability in AD microenvironment. In Aβ1-42-incubated microvascular endothelial cells (ECs) of 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 the BBB permeability via upregulating the levels of tight junction-related proteins. ELK4 was downregulated in BBB model in vitro in AD microenvironment. LINC00662 mediated the degradation of ELK4 mRNA by SMD pathway. The downregulated ELK4 increased the permeability of BTB by inducing the tight junction-related proteins. TRA2A/LINC00662/ELK4 axis is important in the regulation of BBB permeability in AD microenvironment, which would be a new molecular target for AD treatment.
- Published
- 2020