TRA2A-induced upregulation of LINC00662 regulates blood-brain barrier permeability by affecting ELK4 mRNA stability in Alzheimer's microenvironment

Abstract

The blood-brain barrier (BBB) plays a pivotal role 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 involved in the regulation of BBB permeability. Our study was performed to demonstrate TRA2A/LINC00662/ELK4 axis in regulating 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 expressions of tight junction-related proteins. ELK4 was lower expressed 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 increasing the tight junction-related proteins expressions. 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.

TRA2A Binds With LncRNA MALAT1 To Promote Esophageal Cancer Progression By Regulating EZH2/β-catenin Pathway

“…Indeed, another lncRNA, LINC00662, was recently reported to bind with TRA2A. This interaction increases LINC00662 stability, thereby to regulate blood-brain barrier permeability in the Alzheimer's microenvironment [28]. In addition, we have demonstrated that the binding of TRA2A to MALAT1 controls the EZH2/β-catenin pathway in siRNA depletion assay.…”