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

Oncogene volume 36, pages 318–331 (2017)Cite this article

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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.

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Acknowledgements

This work is supported by grants from the Natural Science Foundation of China (81172197, 81272564, 81272795, 81372484 and 81573010) and Shenyang Science and Technology Plan Projects (nos F15-199-1-30 and F15-199-1-57), and outstanding scientific fund of Shengjing hospital (no. 201304).

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Authors and Affiliations

  1. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China

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

  2. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People’s Republic of China

    Y Xue, J Ma & Z Li

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Cai, H., Liu, X., Zheng, J. et al. Long non-coding RNA taurine upregulated 1 enhances tumor-induced angiogenesis through inhibiting microRNA-299 in human glioblastoma. Oncogene 36, 318–331 (2017). https://doi.org/10.1038/onc.2016.212

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