MicroRNA-219-5p exerts tumor suppressor function by targeting ROBO1 in glioblastoma

Tumour Biol. 2015 Nov;36(11):8943-51. doi: 10.1007/s13277-015-3651-4. Epub 2015 Jun 17.

Abstract

Previous studies have shown that miR-219-5p is dysregulated and exerts tumor-suppressive effects in cancer development and progression. However, the molecular function and mechanism of miR-219-5p in glioblastoma growth and invasion are still unclear. In the present study, we show that miR-219-5p was downregulated in a panel of glioma tissues with different grades and in all the human glioma cell lines examined. Ectopic expression of miR-219-5p inhibited proliferation and invasion and induced apoptosis in vitro, and xenograft formation in vivo. ROBO1 was found to be a direct target of miR-219-5p, and when overexpressed in miR-219-5p-expressing glioma cells, was able to restore proliferative and invasive ability. Finally, in vivo investigation confirmed that miR-219-5p was a tumor suppressor that regulated ROBO1 expression. Taken together, these studies demonstrate that miR-219-5p inhibited cancer cell growth and invasion by direct targeting ROBO1, implicating miR-219-5p as an attractive candidate for cancer therapy.

Keywords: Glioblastoma; Invasion; Proliferation; ROBO1; miR-219-5p.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Humans
  • Mice
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / biosynthesis*
  • Receptors, Immunologic / genetics
  • Roundabout Proteins
  • Xenograft Model Antitumor Assays

Substances

  • MIRN219 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • Receptors, Immunologic