HOXC6 promotes migration, invasion and proliferation of esophageal squamous cell carcinoma cells via modulating expression of genes involved in malignant phenotypes.

Background: HOXC6 is a member of the HOX gene family. The elevated expression of this gene occurs in prostate and breast cancers. However, the role of HOXC6 in esophageal squamous cell carcinoma (ESCC) remains largely uninvestigated. Methods: The expression of HOXC6 was examined by immunohistochemistry, quantitative real-time PCR and immunoblotting assays. The lentivirus-mediated expression of HOXC6 was verified at mRNA and protein levels. Wound healing and Matrigel assays were performed to assess the effect of HOXC6 on the migration and invasion of cancer cells. The growth curving, CCK8, and colony formation assays were utilized to access the proliferation capacities. RNA-seq was performed to evaluate the downstream targets of HOXC6. Bioinformatic tool was used to analyze the gene expression. Results: HOXC6 was highly expressed in ESCC tissues. HOXC6 overexpression promoted the migration, invasion, and proliferation of both Eca 109 and TE10 cells. There were 2,155 up-regulated and 759 down-regulated genes in Eca 109-HOXC6 cells and 95 up-regulated and 47 down-regulated genes in TE10-HOXC6 cells compared with the results of control. Interestingly, there were only 20 common genes, including 17 up-regulated and three down-regulated genes with similar changes upon HOXC6 transfection in both cell lines. HOXC6 activated several crucial genes implicated in the malignant phenotype of cancer cells. Discussion: HOXC6 is highly expressed in ESCC and promotes malignant phenotype of ESCC cells. HOXC6 can be used as a new therapeutic target of ESCC.