MicroRNA-101 inhibits proliferation, migration and invasion of human glioblastoma by targeting SOX9

Oncotarget. 2017 Mar 21;8(12):19244-19254. doi: 10.18632/oncotarget.13706.

Abstract

Glioblastoma multiforme (GBM) is the most common primary malignant tumors originating in the brain parenchyma. At present, GBM patients have a poor prognosis despite the continuous progress in therapeutic technologies including surgery, radiotherapy, photodynamic therapy, and chemotherapy. Recent studies revealed that miR-101 was remarkably down-regulated in kinds of human cancers and was associated with aggressive tumor cell proliferation and stem cell self-renewal. Data also showed that miR-101 was down-regulated in primary glioma samples and cell lines, but the underlying molecular mechanism of the deregulation of miR-101 in glioma remained largely unknown. In this study, we found that miR-101 could inhibit the proliferation and invasion of glioma cells both in vitro and in vivo by directly targeting SOX9 [sex-determining region Y (SRY)-box9 protein]. Silencing of SOX9 exerted similar effects with miR-101 overexpression on glioma cells proliferation and invasion. Quantitative reverse transcription PCR and Western blotting analysis revealed a negative relationship between miR-101 and SOX9 in human glioma U251MG and U87MG cells, and the luciferase assay indicated that miR-101 altered SOX9 expression by directly targeting on 3'UTR. Taken together, our findings suggest that miR-101 regulates glioma proliferation, migration and invasion via directly down-regulating SOX9 both in vitro and in vivo, and miR-101 may be a potential therapeutic target for future glioma treatment.

Keywords: MiR-101; SOX9; invasion; migration; proliferation.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Prognosis
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MIRN101 microRNA, human
  • MicroRNAs
  • SOX9 Transcription Factor
  • SOX9 protein, human