MiR-128 inhibits tumor growth and angiogenesis by targeting p70S6K1

PLoS One. 2012;7(3):e32709. doi: 10.1371/journal.pone.0032709. Epub 2012 Mar 19.

Abstract

MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-128 expression levels were decreased in glioma, and identified p70S6K1 as a novel direct target of miR-128. Overexpression of miR-128 suppressed p70S6K1 and its downstream signaling molecules such as HIF-1 and VEGF expression, and attenuated cell proliferation, tumor growth and angiogenesis. Forced expression of p70S6K1 can partly rescue the inhibitory effect of miR-128 in the cells. Taken together, these findings will shed light to the role and mechanism of miR-128 in regulating glioma tumor angiogenesis via miR-128/p70S6K1 axis, and miR-128 may serve as a potential therapeutic target in glioma in the future.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Glioma / enzymology*
  • Glioma / genetics
  • Glioma / therapy
  • Humans
  • Hypoxia-Inducible Factor 1 / biosynthesis
  • Hypoxia-Inducible Factor 1 / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / enzymology*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / therapy
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction / genetics
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Hypoxia-Inducible Factor 1
  • MIRN128 microRNA, human
  • MicroRNAs
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Ribosomal Protein S6 Kinases, 70-kDa