MiR-137 inhibits proliferation and angiogenesis of human glioblastoma cells by targeting EZH2

It is suggested that microRNAs play important roles in the development of various cancers. Here, we showed that miR-137 is downregulated in glioblastoma (GBM) cell lines and that low levels of miR-137 are associated with a poor prognostic phenotype of GBM patients. Ectopic expression of miR-137 sign...

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Bibliographic Details
Published in:Journal of neuro-oncology 2015-05, Vol.122 (3), p.481-489
Main Authors: Sun, Jie, Zheng, Guodong, Gu, Zhengtao, Guo, Zhenhui
Format: Article
Language:English
Subjects:
Animals
Brain Neoplasms - drug therapy
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Cell Line, Tumor
Cell Proliferation
Enhancer of Zeste Homolog 2 Protein
Female
Gene Expression Regulation, Neoplastic - drug effects
Gene Expression Regulation, Neoplastic - genetics
Gene Expression Regulation, Neoplastic - physiology
Glioblastoma - drug therapy
Glioblastoma - metabolism
Glioblastoma - pathology
Humans
Laboratory Investigation
Male
Medicine
Medicine & Public Health
Mice
Mice, SCID
MicroRNAs - genetics
MicroRNAs - metabolism
Neovascularization, Pathologic - drug therapy
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - metabolism
Neurology
Oncology
Polycomb Repressive Complex 2 - genetics
Polycomb Repressive Complex 2 - metabolism
RNA, Messenger - metabolism
Transfection
Xenograft Model Antitumor Assays
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Description
Summary:It is suggested that microRNAs play important roles in the development of various cancers. Here, we showed that miR-137 is downregulated in glioblastoma (GBM) cell lines and that low levels of miR-137 are associated with a poor prognostic phenotype of GBM patients. Ectopic expression of miR-137 significantly inhibited GBM cell proliferation and angiogenesis. In addition, ectopic expression of miR-137 inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. EZH2 was identified as a direct target of miR-137 by using luciferase reporter and Western blot assays, and EZH2 overexpression can rescue the inhibitory effect of miR-137 on cell proliferation and angiogenesis. Furthermore, tumor samples from GBM patients showed an inverse relationship between miR-137 and EZH2 levels. Our results suggest that miR-137 may serve as a biomarker in GBM, and the modulation of its activity may represent a novel therapeutic strategy for the treatment of GBM patients.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-015-1753-x