HOXC 10 promotes proliferation and invasion and induces immunosuppressive gene expression in glioma

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 HOXC 10 in regulating immunosuppressive gene expression in glioma cell lines and their proliferative and invasive capacities. Although HOXC 10 expression is dysregulated in several types of tumors, its potential function in glioma was not known. We found that HOXC 10 expression was upregulated in glioma compared with normal tissue, and that HOXC 10 expression positively associated with high grading of glioma. In three independent datasets ( REMBRANDT glioma, The Cancer Genome Atlas glioblastoma multiforme and GSE 4412), HOXC 10 upregulation was associated with short overall survival. In two glioma cell lines, HOXC 10 knock‐down inhibited cell proliferation, colony formation, migration and invasion, and promoted apoptosis. In addition, HOXC 10 knock‐down suppressed the expression of genes that are involved in tumor immunosuppression, including those for transforming growth factor‐β 2, PD ‐L2, CCL 2 and TDO 2. A ChIP assay showed that HOXC 10 directly bound to the PD ‐L2 and TDO 2 promoter regions. In summary, our results suggest that HOXC 10 upregulation in glioma promotes an aggressive phenotype and induces immunosuppressive gene expression, supporting further investigation of the potential of HOXC 10 as a therapeutic target in glioma.