Abstract
Background: RNA binding protein have recently emerged as critical regulators of various biologic processes and therapeutic targets. RNA-binding Fox 1(RBFOX1) involved in in non-small cell lung cancer progress. However, there is no research about the functional role of RBFOX1 in glioma endothelial cells (GECs). Methods: The in vitro blood-tumor barrier (BTB) model and RBFOX1 overexpressed or silenced GECs were established. Transendothelial electric resistance (TEER) measurements and HRP flux assays to detect the integrity and permeability of BTB. Immunofluorescence and Chromatin Immunoprecipitation (ChIP) assays were used to detect the potential mechanism. Findings: RBFOX1 was downregulation in GECs. Overexpression of RBFOX1 resulted in an impaired integrity and increased permeability of BTB and decreased the tight-related protein zonula occludin (ZO)-1, occludin, claudin-5 expression. Long non-coding RNA linc00673, was targets of RBFOX1, knockdown increased BTB permeability and destabilized MAFF mRNA through Staufen 1-mediated messenger RNA decay (SMD). MAFF bound to the promoter regions and inhibited the promoter activity of ZO-1, occludin, and claudin-5 in GECs. Interpretation: Those results indicated the potential role of RBFOX1/linc00673/MAFF pathway in regulation of BTB permeability, thereby may provide new targets of glioma therapy. Funding Statement This work is supported by grants from the Natural Science Foundation of China (81573010, 81672511 and 81602726), Liaoning Science and Technology Plan Project (No. 2017225020, 2015225007), Project of Key Laboratory of Neuro-oncology in Liaoning Province (112-2400017005), special developmental project guided by central government of Liaoning Province (No. 2017011553-301). Declaration of Interests: The authors declared that they have no conflict of interest. Ethics Approval Statement: All the participants signed and provided the informed consent, and this study was approved by the Institutional Review Board of Shengjing Hospital of China Medical University.
Published Version
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