title: MiR-34a regulates blood-tumor barrier function by targeting protein kinase Cε.
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 function by targeting PKCε; after phosphorylation, PKCε is activated and contributes to regulation of the expression of tight junction-related proteins, ultimately altering BTB permeability.
authors: Department of Neurobiology, China Medical University, Shenyang 110122, China Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110122, China.
authors: Wei
authors: W
authors: Zhao
authors: Department of Neurobiology, China Medical University, Shenyang 110122, China Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110122, China.
authors: Ping
authors: P
authors: Wang
authors: Department of Neurobiology, China Medical University, Shenyang 110122, China Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110122, China.
authors: Jun
authors: J
authors: Ma
authors: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors: Yun-Hui
authors: YH
authors: Liu
authors: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors: Zhen
authors: Z
authors: Li
authors: Department of Neurobiology, China Medical University, Shenyang 110122, China Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110122, China.
authors: Zhi-Qing
authors: ZQ
authors: Li
authors: Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, China.
authors: Zhen-Hua
authors: ZH
authors: Wang
authors: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors: Liang-Yu
authors: LY
authors: Chen
authors: Department of Neurobiology, China Medical University, Shenyang 110122, China Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110122, China xueyixue888@163.com.
authors: Yi-Xue
authors: YX
authors: Xue
mesh_terms: D002199:Capillary Permeability / Q000235:genetics; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051744:Protein Kinase C-epsilon / Q000235:genetics*; D015398:Signal Transduction; D062725:Tight Junction Proteins / Q000235:genetics; D015854:Up-Regulation
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D062725:Tight Junction Proteins; C497255:PRKCE protein, human; D051744:Protein Kinase C-epsilon