title: The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Physiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Shang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability; D002460:Cell Line; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D017097:Electric Impedance; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C107466:CLDN5 protein, human; D062507:Claudin-5; D006360:Heat-Shock Proteins; C554293:MIRN144 microRNA, human; D035683:MicroRNAs; C568985:OCLN protein, human; D062793:Occludin; D062085:RNA, Long Noncoding; C569042:TJP1 protein, human; C000598536:TUG1 long noncoding RNA, human; D014157:Transcription Factors; D062826:Zonula Occludens-1 Protein; C070389:HSF2 protein, human
keywords: HSF2; TUG1; blood-tumor barrier; glioma; microRNA-144