MiR-34a regulates blood-tumor barrier function by targeting protein kinase Cε

Molecular Biology of the Cell
Wei ZhaoYi-xue Xue

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 Cε (PKCε) reduction. Moreover, luciferase reporter gene analysis shows that PKCε is the target gene of miR-34a. We also show that cotransfection of miR-34a and PKCε inversely coregulates BTB permeability and protein expression levels of tight junction-related proteins. Pretreatment of ψεRACK, a PKCε-specific activator, decreases BTB permeability in miR-34a-overexpressed GECs and up-regulates expression levels of tight junction proteins. In contrast, pretreatment of εV1-2, a specific PKCε inhibitor, gives opposite results. Collectively, our findings indicate that miR-34a regulates BTB fu...Continue Reading

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Citations

Dec 15, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Mimi BukeiratXuefang Ren
Dec 21, 2017·International Journal of Molecular Sciences·Gabriella SchieraItalia Di Liegro
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Jul 14, 2017·Frontiers in Molecular Neuroscience·Libo SaYixue Xue
Nov 30, 2018·Journal of Molecular Neuroscience : MN·Christelle En Lin Chua, Bor Luen Tang
Jul 7, 2017·Oxidative Medicine and Cellular Longevity·Juhyun SongOh Yoen Kim
Feb 26, 2020·Scientific Reports·Heng HuXuefang Ren

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Methods Mentioned

BETA
PCR
transfection
reverse transcription PCR
electrophoresis
Assay
Protein Assay

Software Mentioned

Fluor Chem
TargetScan
SPSS
TargetScan Human
Fluor Chen

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