MicroRNA-301b promotes the proliferation and invasion of glioma cells through enhancing activation of Wnt/β-catenin signaling via targeting Glypican-5

Eur J Pharmacol. 2019 Jul 5:854:39-47. doi: 10.1016/j.ejphar.2019.03.057. Epub 2019 Apr 3.

Abstract

Accumulating evidence has suggested that Glypican-5 (GPC5) is a tumor suppressor gene in many types of cancers. However, whether GPC5 is involved in glioma remains unknown. This study was designed to explore the expression, biological function and regulatory mechanism of GPC5 in glioma. Our results demonstrated that GPC5 expression was significantly decreased in multiple glioma cell lines. Gain-of-function experiments showed that the ectopic expression of GPC5 markedly inhibited the proliferation, invasion and Wnt/β-catenin signaling of glioma cell lines. GPC5 was identified as a target gene of microRNA-301b (miR-301b). Further data showed that miR-301b expression was significantly up-regulated in glioma tissues and cell lines. In addition, miR-301b expression was inversely correlated with GPC5 expression in clinical glioma tissues. The overexpression of miR-301b promoted the proliferation, invasion and Wnt/β-catenin signaling of glioma cell lines, whereas the inhibition of miR-301b showed the opposite effect. However, the silencing of GPC5 significantly reversed the antitumor effect of miR-301b inhibition. Overall, our results revealed a tumor suppressive role of GPC5 in glioma and suggested that GPC5 expression was regulated by miR-301b. Our study indicates that the inhibition of miR-301b represses the proliferation and invasion of glioma cells by up-regulating GPC5 expression.

Keywords: GPC5; Glioma; miR-301b.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioma / pathology*
  • Glypicans / deficiency
  • Glypicans / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Wnt Signaling Pathway / genetics*

Substances

  • GPC5 protein, human
  • Glypicans
  • MIRN301A microRNA, human
  • MicroRNAs