4.1 Article

PVT1 affects growth of glioma microvascular endothelial cells by negatively regulating miR-186

Journal

TUMOR BIOLOGY
Volume 39, Issue 3, Pages -

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1177/1010428317694326

Keywords

Glioma; angiogenesis; PVT1; miR-186; endothelial cells

Categories

Funding

  1. Natural Science Foundation of China [81672511, 81573010, 81372484]
  2. Liaoning Science and Technology Plan Project [2015225007]
  3. Shenyang Science and Technology Plan Projects [F15-199-1-30, F15-199-1-57]
  4. outstanding scientific fund of Shengjing hospital [201304]

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Vigorous angiogenesis is one of the reasons for the poor prognosis of glioma. A number of studies have shown that long non-coding RNA can affect a variety of biological behaviors of tumors. However, the influence of long non-coding RNAs on glioma vascular endothelial cells remains unclear. To simulate the glioma microenvironment, we applied glioma-conditioned medium to human cerebral microvascular endothelial cells. The long non-coding RNA PVT1 was found to be highly expressed in glioma vascular endothelial cells. Cell Counting Kit-8, migration, and tube formation assays showed that PVT1 overexpression promoted glioma vascular endothelial cells proliferation, migration, and angiogenesis. We also found that PVT1 overexpression upregulated the expression of the autophagy-related proteins Atg7 and Beclin1, which induced protective autophagy. Bioinformatics software and dual-luciferase system analysis confirmed that PVT1 acts by targeting miR-186. In addition, our study showed that miR-186 could target the 3' untranslated region of Atg7 and Beclin1 to decrease their expression levels, thereby inhibiting glioma-conditioned human cerebral microvascular endothelial cell autophagy. In conclusion, PVT1 overexpression increased the expression of Atg7 and Beclin1 by targeting miR-186, which induced protective autophagy, thus promoting glioma vascular endothelial cell proliferation, migration, and angiogenesis. Therefore, PVT1 and miR-186 can provide new therapeutic targets for future anti-angiogenic treatment of glioma.

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