title: Long non-coding RNA taurine upregulated 1 enhances tumor-induced angiogenesis through inhibiting microRNA-299 in human glioblastoma.
abstract: Angiogenesis is one of the critical biological elements affecting the development and progression of cancer. Long non-coding RNAs (lncRNAs) are important regulators and aberrantly expressed in various types of human cancer. Our previous studies indicated that lncRNA taurine upregulated 1 (TUG1) implicated in the regulation of blood-tumor barrier permeability; however, its role in glioblastoma angiogenesis still unclear. Here we demonstrated that TUG1 was up-expressed in human glioblastoma tissues and glioblastoma cell lines. Knockdown of TUG1 remarkably suppressed tumor-induced endothelial cell proliferation, migration and tube formation as well as reducing spheroid-based angiogenesis ability in vitro, which are the critical steps for tumor angiogenesis. Besides, knockdown of TUG1 significantly increased the expression of mircroRNA-299 (miR-299), which was down-expressed in glioblastoma tissues and glioblastoma cell lines. Bioinformatics analysis and luciferase reporter assay revealed that TUG1 influenced tumor angiogenesis via directly binding to the miR-299 and there was a reciprocal repression between TUG1 and miR-299 in the same RNA-induced silencing complex. Moreover, knockdown of TUG1 reduced the expression of vascular endothelial growth factor A (VEGFA), which was defined as a functional downstream target of miR-299. In addition, knockdown of TUG1, shown in the in vivo studies, has effects on suppressing tumor growth, reducing tumor microvessel density and decreasing the VEGFA expression by upregulating miR-299 in xenograft glioblastoma model. Overall, the results demonstrated that TUG1 enhances tumor-induced angiogenesis and VEGF expression through inhibiting miR-299. Also, the inhibition of TUG1 could provide a novel therapeutic target for glioblastoma treatment.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: Z
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: Z
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Z
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: M
authors.initials: M
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C553452:MIRN299 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C000598536:TUG1 long noncoding RNA, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A