MicroRNA-200b inhibits the growth and metastasis of glioma cells via targeting ZEB2

Int J Oncol. 2016 Feb;48(2):541-50. doi: 10.3892/ijo.2015.3267. Epub 2015 Nov 26.

Abstract

MicroRNAs (miRs) have been found to play important roles in mediating a variety of biological processes in human cancers, including tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). In the present study, we aimed to investigate the putative role of miR‑200b in the progression of glioma. Real-time RT-PCR data showed that the miR‑200b levels were frequently reduced in primary glioma tissues (n=88) and cell lines, when compared to normal brain tissues (n=25). Moreover, decreased miR‑200b level was tightly associated with the malignant progression of glioma. Overexpression of miR‑200b significantly suppressed cell proliferation, migration, invasion and EMT in glioma U251 and U87 cells. Luciferase reporter assay data further identified ZEB2 as a direct target of miR‑200b, and the protein expression of ZEB2 was markedly reduced after overexpression of miR‑200b in U251 and U87 cells. Furthermore, restoration of ZEB2 effectively reversed the reduced expression of ZEB2, as well as the suppressive effects of miR‑200b overexpression on the proliferation, migration, invasion and EMT in glioma U251 and U87 cells. Moreover, in vivo study showed that overexpression of miR‑200b significantly inhibited tumorigenesis as well as the tumor growth of glioma cells, and effectively protected nude mice from tumor-induced death. Taken together these findings suggest that miR‑200b has suppressive effects on the proliferation, migration, invasion and EMT of glioma cells, partly at least, via targeting ZEB2. Therefore, miR‑200b acts as a novel tumor suppressor in glioma, and thus may become a promising therapeutic candidate for glioma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics
  • Brain Neoplasms / genetics
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Tumor Suppressor / physiology
  • Glioma / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics*
  • Repressor Proteins / genetics*
  • Young Adult
  • Zinc Finger E-box Binding Homeobox 2

Substances

  • Homeodomain Proteins
  • MIRN200 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2