MicroRNA-26a promotes tumor growth and angiogenesis in glioma by directly targeting prohibitin

CNS Neurosci Ther. 2013 Oct;19(10):804-12. doi: 10.1111/cns.12149. Epub 2013 Jul 22.

Abstract

Backgrounds and aims: Glioma accounts for the majority of primary malignant brain tumors in adults. Upregulation of microRNA-26a (miR-26a) has been observed in glioma. However, the biological function and molecular mechanism of miR-26a in glioma remain to be elucidated.

Methods: Glioma cells stably overexpressing or down-expressing miR-26a were analyzed for both in vitro and in vivo biological functions. Novel target of miR-26a was identified by bioinformatics searching and molecular biological assays. Glioma specimens and normal brain tissues were analyzed for both expression levels of miR-26a and its target.

Results: Forced expression of miR-26a in glioma cells significantly increased both growth rate and colony formation in vitro and tumor growth and angiogenesis in vivo, while reduced expression of miR-26a played opposite roles. MiR-26a directly targeted prohibitin (PHB) whose expression levels were downregulated in glioma specimens. The levels of miR-26a were inversely correlated with PHB expression levels in glioma samples and strongly correlated with clinical WHO grades of glioma.

Conclusion: These results reveal that miR-26a regulates PHB and promotes glioma progression both in vitro and in vivo and that miR-26a and its target PHB are associated with glioma development, which can be helpful in developing microRNA-based treatment for glioma in the future.

Keywords: Angiogenesis; Glioma; MicroRNA-26a; Prohibitin; Tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression*
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis*
  • Neovascularization, Pathologic / metabolism*
  • Prohibitins
  • Receptor, EphB3
  • Repressor Proteins / biosynthesis*

Substances

  • MIRN26A microRNA, human
  • MicroRNAs
  • PHB protein, human
  • Prohibitins
  • Repressor Proteins
  • Receptor, EphB3