Decreased miRNA-637 is an unfavorable prognosis marker and promotes glioma cell growth, migration and invasion via direct targeting Akt1

Oncogene. 2015 Sep 17;34(38):4952-63. doi: 10.1038/onc.2014.419. Epub 2015 Jan 19.

Abstract

Although increasing evidence indicated that the deregulation of microRNAs (miRNAs) contributes to tumorigenesis and invasion, little is known about the role of miR-637 in human gliomas. In the present study, we found that the expression level of miR-637 was significantly reduced in clinical glioma tissues compared with normal brain tissues. Moreover, we revealed that the introduction of miR-637 dramatically suppressed glioma cell growth, migration and invasion in vitro and in vivo. Further studies revealed that Akt1 is a direct target gene of miR-637. Silencing of Akt1 inhibited the growth and invasion of glioma cells by decreasing phosphorylated Akt, β-catenin, phosphorylated Foxo1 and Cyclin D1 and inducing the expression of Foxo1, which was consistent with the effect of miR-637 overexpression. Suppressed expression of miR-637 and increased Akt1 protein levels were correlated with unfavorable progression and poor prognosis, respectively, and a negative relationship between the miR-637 expression and Akt1 protein levels was observed in gliomas. Our findings provide new insights into the role of miR-637 in the development of gliomas, and implicate the potential application of miR-637 in cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Proliferation
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phosphorylation
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • MIRN637 microRNA, human
  • MicroRNAs
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt