MiR-638 serves as a tumor suppressor by targeting HOXA9 in glioma

Eur Rev Med Pharmacol Sci. 2018 Nov;22(22):7798-7806. doi: 10.26355/eurrev_201811_16404.

Abstract

Objective: MiR-638 is constantly downregulated and serves as a tumor suppressor in various cancers. Its role in gliomas remains unclear. This study is designed to investigate the clinical significance and the pathogenic role of miR-638 in human gliomas.

Patients and methods: Quantitative Real-time PCR was performed to analyze the expression of miR-638 in the tumor and adjacent tissues of 24 glioma patients. The association between the expression of miR-638 and clinical features were examined. Survival of patients was studied by Kaplan-Meier curves. The impact of miR-638 on cell growth and apoptosis was determined by CCK-8 assay, colony formation assay, cell cycle analysis and Annexin V-FITC-PI apoptosis assay. The effect of miR-638 on HOXA9 was determined by luciferase assay and Western blot. The effect of miR-638 and HOXA9 on expression of oncogenes, Cyclin D1 and C-MYC was determined by Western blot.

Results: MiR-638 expression was constantly downregulated in glioma tumor tissue, which is negatively correlated with the WHO grade. MiR-638 expression was associated with clinical features such as tumor size, KPS score and WHO grade. Patients with low miR-638 had a worse overall survival than those with high expression. Experimentally, miR-638 directly targeted HOXA9 to suppress its expression, leading to attenuations of cell proliferation, colony formation and cell cycle progression and enhanced basal apoptosis level. MiR-638/HOXA9 axis also suppressed the expression of Wnt/beta-catenin-regulated oncogenes, Cyclin D1 and C-MYC.

Conclusions: MiR-638 is a constantly downregulated microRNA in gliomas and is associated with its prognosis. MiR-638 regulates cellular malignancy of gliomas through targeting HOXA9. Thus, miR-638/HOXA9 signaling axis may have therapeutic potential in gliomas.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin D1 / metabolism
  • Down-Regulation
  • Female
  • Genes, Tumor Suppressor
  • Glioma / genetics*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • Signal Transduction
  • beta Catenin / metabolism

Substances

  • CCND1 protein, human
  • CTNNB1 protein, human
  • Homeodomain Proteins
  • MIRN638 microRNA, human
  • MicroRNAs
  • beta Catenin
  • homeobox protein HOXA9
  • Cyclin D1