MiR-34a regulates blood-tumor barrier function by targeting protein kinase C?.

ABSTRACT: MicroRNA-34a (miR-34a) functions to regulate protein expression at the posttranscriptional level by binding the 3' UTR of target genes and regulates functions of vascular endothelial cells. However, the role of miR-34a in regulating blood-tumor barrier (BTB) permeability remains unknown. In this study, we show that miR-34a overexpression leads to significantly increased permeability of BTB, whereas miR-34a silencing reduces the permeability of the BTB. In addition, miR-34a overexpression significantly down-regulates the expression and distribution of tight junction-related proteins in glioma endothelial cells (GECs), paralleled by protein kinase C? (PKC?) reduction. Moreover, luciferase reporter gene analysis shows that PKC? is the target gene of miR-34a. We also show that cotransfection of miR-34a and PKC? inversely coregulates BTB permeability and protein expression levels of tight junction-related proteins. Pretreatment of ??RACK, a PKC?-specific activator, decreases BTB permeability in miR-34a-overexpressed GECs and up-regulates expression levels of tight junction proteins. In contrast, pretreatment of ?V1-2, a specific PKC? inhibitor, gives opposite results. Collectively, our findings indicate that miR-34a regulates BTB function by targeting PKC?; after phosphorylation, PKC? is activated and contributes to regulation of the expression of tight junction-related proteins, ultimately altering BTB permeability.

SUBMITTER: Zhao W 

PROVIDER: S-EPMC4436826 | biostudies-other | 2015 May

REPOSITORIES: biostudies-other