Journal Article

Long non-coding RNA taurine upregulated 1 enhances tumor-induced angiogenesis through inhibiting microRNA-299 in human glioblastoma

Bao, M, Liu, Y, Liu, X, Cai, H, Xue, Y, Li, Z, Ma, J, Xi, Z, Zheng, J

2017

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/109 / 13/51 / 13/89 / 3' Untranslated Regions / 42/44 / 631/337/384 / 631/67/2328 / 64/60 / Analysis / Angiogenesis / Animals / Apoptosis / Blood-vessels / Brain Neoplasms - genetics / Brain Neoplasms - metabolism / Brain Neoplasms - pathology / Cancer / Care and treatment / Cell Biology / Cell Line, Tumor / Cell Proliferation / Development and progression / Gene expression / Gene Expression Regulation, Neoplastic / Gene Knockdown Techniques / Gene silencing / Genetic aspects / Glioblastoma - genetics / Glioblastoma - metabolism / Glioblastoma - pathology / Glioblastoma multiforme / Health aspects / Human Genetics / Humans / Internal Medicine / Medicine / Medicine & Public Health / Mice / MicroRNAs - genetics / Neoplasm Transplantation / Neovascularization / Oncology / Oncology, Experimental / original-article / Ribonucleic acid / RNA / RNA, Long Noncoding - genetics / Studies / Tumors / Up-Regulation / Vascular Endothelial Growth Factor A - genetics / Vascular Endothelial Growth Factor A - secretion