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Front Mol Neurosci. 2017 Sep 21;10:301. doi: 10.3389/fnmol.2017.00301. eCollection 2017.

Transcription Factor NFAT5 Promotes Glioblastoma Cell-driven Angiogenesis via SBF2-AS1/miR-338-3p-Mediated EGFL7 Expression Change.

Yu H1,2,3, Zheng J1,2,3, Liu X1,2,3, Xue Y4,5, Shen S4,5, Zhao L4,5, Li Z1,2,3, Liu Y1,2,3.

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Department of Neurosurgery, Shengjing Hospital of China Medical UniversityShenyang, China.
Liaoning Research Center for Clinical Medicine in Nervous System DiseaseShenyang, China.
Key laboratory of Neuro-oncology in Liaoning ProvinceShenyang, China.
Department of Neurobiology, College of Basic Medicine, China Medical UniversityShenyang, China.
Key Laboratory of Cell Biology, Ministry of Public Health of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of ChinaShenyang, China.


Glioblastoma (GBM) is the most aggressive primary intracranial tumor of adults and confers a poor prognosis due to high vascularization. Hence anti-angiogenic therapy has become a promising strategy for GBM treatment. In this study, the transcription factor nuclear factor of activated T-cells 5 (NFAT5) was significantly elevated in glioma samples and GBM cell lines, and positively correlated with glioma WHO grades. Knockdown of NFAT5 inhibited GBM cell-driven angiogenesis. Furthermore, long non-coding RNA SBF2 antisense RNA 1 (SBF2-AS1) was upregulated in glioma samples and knockdown of SBF2-AS1 impaired GBM-induced angiogenesis. Downregulation of NFAT5 decreased SBF2-AS1 expression at transcriptional level. In addition, knockdown of SBF2-AS1 repressed GBM cell-driven angiogenesis via enhancing the inhibitory effect of miR-338-3p on EGF like domain multiple 7 (EGFL7). In vivo study demonstrated that the combination of NFAT5 knockdown and SBF2-AS1 knockdown produced the smallest xenograft volume and the lowest microvessel density. NFAT5/SBF2-AS1/miR-338-3p/EGFL7 pathway may provide novel targets for glioma anti-angiogenic treatment.


EGFL7; NFAT5; SBF2-AS1; glioblastoma angiogenesis; long non-coding RNA; miR-338-3p; transcription factor

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