MicroRNA-200b-3p suppresses epithelial-mesenchymal transition and inhibits tumor growth of glioma through down-regulation of ERK5

Biochem Biophys Res Commun. 2016 Sep 23;478(3):1158-64. doi: 10.1016/j.bbrc.2016.08.085. Epub 2016 Aug 18.

Abstract

Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development of cancer. Has-miR-200b-3p is generally recognized as one of the fundamental regulators of EMT. In this study, we found that the expression of miR-200b-3p was downregulated in glioma tissues and human glioma cells U87 and U251. Meanwhile, Up-regulating miR-200b-3p enhanced E-cadherin, reduced mesenchymal markers, and decreased cell proliferation, migration, and invasion in vitro. In vivo, the xenograft mouse model also unveiled the suppressive effects of miR-200b-3p on tumor growth. Additionally, The extracellular-regulated protein kinase 5 (ERK5) was confirmed as a direct target gene of miR-200b-3p. The direct suppression of ERK5 expressions by miR-200b-3p was revealed by luciferase reporter assay, quantitative RT-PCR analysis, and western blot. Moreover, we observed an inverse correlation between miR-200b-3p and ERK5 in human glioma tissues. In summary, our findings demonstrated that miR-200b-3p suppresses glioma tumor growth, invasion, and reverses EMT through downregulated its target ERK5.

Keywords: EMT; ERK5; Glioma; Has-miR-200b-3p (miR-200b-3p); Invasion.

MeSH terms

  • Animals
  • Base Sequence
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation / genetics*
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / pathology*
  • HEK293 Cells
  • Humans
  • Mice, SCID
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 7 / genetics*
  • Mitogen-Activated Protein Kinase 7 / metabolism
  • Neoplasm Invasiveness

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • Mitogen-Activated Protein Kinase 7