MiR-429 Regulated by Endothelial Monocyte Activating Polypeptide-II (EMAP-II) Influences Blood-Tumor Barrier Permeability by Inhibiting the Expressions of ZO-1, Occludin and Claudin-5.

摘要: The blood-tumor barrier (BTB) hinders delivery of chemotherapeutic drugs to tumors in the brain; previous studies have shown that BTB can be selectively opened by endothelial monocyte activating polypeptide-II (EMAP-II), but specific mechanism involved remains elusive. In this study, we found microRNA-429 (miR-429) expression glioma vascular cells (GECs) was far lower than human brain microvascular (ECs). miR-429 had GECs and tissues compared ECs or normal brain. Furthermore, high grade (HGG) low (LGG). vitro models, also EMAP-II significantly increased permeability, decreased ZO-1, occludin claudin-5 GECs, a time- dose-dependent manner. greatly models vitro. Overexpression transepithelial electric resistance (TEER) values led enhanced horseradish peroxidase (HRP) flux. tight junction (TJ)-associated proteins (ZO-1, claudin-5), distribution continuity. Silencing TJ-associated dual-luciferase reporter assay revealed ZO-1 were target genes miR-429, demonstrated overexpression markedly down-regulated protein p70S6K, as well its phosphorylation levels. showed p70S6K gene miR-429; levels S6 permeability. Conversely, silencing S6, while decreasing conclusion, results indicated caused an increase directly targeted proteins, which negatively regulated; on other hand, targeting regulated. As result, permeability increased.