HOXC10 promotes proliferation and invasion and induces immunosuppressive gene expression in glioma

FEBS J. 2018 Jun;285(12):2278-2291. doi: 10.1111/febs.14476. Epub 2018 May 25.


The prognosis for patients with malignant glioma is very poor and thus the identification of new potential therapeutic targets is critically important. In this work, we report a previously unknown role for the homeobox transcription factor HOXC10 in regulating immunosuppressive gene expression in glioma cell lines and their proliferative and invasive capacities. Although HOXC10 expression is dysregulated in several types of tumors, its potential function in glioma was not known. We found that HOXC10 expression was upregulated in glioma compared with normal tissue, and that HOXC10 expression positively associated with high grading of glioma. In three independent datasets (REMBRANDT glioma, The Cancer Genome Atlas glioblastoma multiforme and GSE4412), HOXC10 upregulation was associated with short overall survival. In two glioma cell lines, HOXC10 knock-down inhibited cell proliferation, colony formation, migration and invasion, and promoted apoptosis. In addition, HOXC10 knock-down suppressed the expression of genes that are involved in tumor immunosuppression, including those for transforming growth factor-β 2, PD-L2, CCL2 and TDO2. A ChIP assay showed that HOXC10 directly bound to the PD-L2 and TDO2 promoter regions. In summary, our results suggest that HOXC10 upregulation in glioma promotes an aggressive phenotype and induces immunosuppressive gene expression, supporting further investigation of the potential of HOXC10 as a therapeutic target in glioma.

Keywords: HOXC10; glioma; immunosuppression; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / immunology
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / immunology
  • Databases, Genetic
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Glioblastoma / genetics*
  • Glioblastoma / immunology
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / immunology
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Programmed Cell Death 1 Ligand 2 Protein / genetics*
  • Programmed Cell Death 1 Ligand 2 Protein / immunology
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Survival Analysis
  • Transforming Growth Factor beta2 / genetics
  • Transforming Growth Factor beta2 / immunology
  • Tryptophan Oxygenase / genetics*
  • Tryptophan Oxygenase / immunology


  • CCL2 protein, human
  • Chemokine CCL2
  • HOXC10 protein, human
  • Homeodomain Proteins
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • RNA, Small Interfering
  • Transforming Growth Factor beta2
  • Tryptophan Oxygenase
  • Luciferases