The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144
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Heng Cai1, Yixue Xue2,3, Ping Wang2,3, Zhenhua Wang4, Zhen Li1, Yi Hu1, Zhiqing Li2,3, Xiuli Shang5 and Yunhui Liu1
1 Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
2 Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People’s Republic of China
3 Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People’s Republic of China
4 Department of Physiology, College of Basic Medicine, China Medical University, Shenyang, People’s Republic of China
5 Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China
Yunhui Liu, email:
Keywords: glioma, TUG1, microRNA-144, blood-tumor barrier, HSF2
Received: February 02, 2015 Accepted: May 25, 2015 Published: June 02, 2015
Blood-tumor barrier (BTB) limits the delivery of chemotherapeutic agent to brain tumor tissues. Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in various biologic processes of tumors. However, the role of lncRNAs in BTB permeability is unclear. LncRNA TUG1 (taurine upregulated gene 1) was highly expressed in glioma vascular endothelial cells from glioma tissues. It also upregulated in glioma co-cultured endothelial cells (GEC) from BTB model in vitro. Knockdown of TUG1 increased BTB permeability, and meanwhile down-regulated the expression of the tight junction proteins ZO-1, occludin, and claudin-5. Both bioinformatics and luciferase reporter assays demonstrated that TUG1 influenced BTB permeability via binding to miR-144. Furthermore, Knockdown of TUG1 also down-regulated Heat shock transcription factor 2 (HSF2), a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of miR-144. HSF2 up-regulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. In conclusion, our results indicate that knockdown of TUG1 increased BTB permeability via binding to miR-144 and then reducing EC tight junction protein expression by targeting HSF2. Thus, TUG1 may represent a useful future therapeutic target for enhancing BTB permeability.
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