Decreased expression of SOX9 indicates a better prognosis and inhibits the growth of glioma cells by inducing cell cycle arrest

Int J Clin Exp Pathol. 2015 Sep 1;8(9):10130-8. eCollection 2015.

Abstract

Deregulation of SOX9 expression has been detected in various human cancer tissues; however, the functional role of SOX9 expression has not been fully elucidated in glioma. SOX9 expression in glioma tissues was analyzed using public tumor datasets and quantitative reverse transcription polymerase chain reaction. The association of SOX9 expression with clinical prognosis in glioma patients was analyzed by examining publically available microarray profiling datasets. The functional roles of SOX9 in glioma were examined using gene set enrichment analysis (GSEA). Cell growth was measured using soft agar colony formation assay, and the cell cycle was analyzed using flow cytometry. Our data showed that SOX9 expression was commonly upregulated in glioma tissues, and patients with high SOX9 levels had shorter survival times. GSEA identified that the gene sets regulating cell proliferation and cell cycle progression were significantly enriched in glioma cells with high SOX9 expression. SOX9 downregulation decreased cyclin D1, CDK4 expression and Rb phosphorylation, which correlated with a reduced population of cells in the S phase and suppressed growth. SOX9, as an oncogene, is highly expressed in gliomas and may be potential indicators of a poor prognosis in glioma patients. SOX9 knockdown may suppress cancer cell growth by inducing cell cycle arrest, which suggests that SOX9 is a potential therapeutic target in glioma.

Keywords: SOX9; cell cycle; glioma; prognosis; proliferation.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cell Cycle Checkpoints / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / mortality
  • Glioma / pathology
  • Humans
  • Male
  • Middle Aged
  • Phosphorylation
  • Prognosis
  • Retinoblastoma Protein / metabolism
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*
  • Survival Rate
  • Up-Regulation

Substances

  • Retinoblastoma Protein
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Cyclin D1
  • Cyclin-Dependent Kinase 4