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

Tumour Biol. 2017 Mar;39(3):1010428317694326. doi: 10.1177/1010428317694326.

Abstract

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.

Keywords: Glioma; PVT1; angiogenesis; endothelial cells; miR-186.

MeSH terms

  • Autophagy / genetics
  • Autophagy-Related Protein 7 / biosynthesis*
  • Beclin-1 / biosynthesis*
  • Beclin-1 / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Endothelial Cells / pathology
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neovascularization, Pathologic / genetics
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics*
  • Transfection

Substances

  • Beclin-1
  • MIRN186 microRNA, human
  • MicroRNAs
  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding
  • Atg7 protein, human
  • Autophagy-Related Protein 7