HOXC12 promotes the invasion and migration of gastric cancer cells by upregulating SALL4 and activating Wnt/β-catenin signaling pathway.

BACKGROUND: Gastric cancer is one of the most common malignant tumors in the world, with a poor prognosis. HOXC is a family of transcription factors that are up-regulated in gastric cancer tissues. However, the relationship between Homeobox C12 (HOXC12) and gastric cancer is still unclear. METHODS: TCGA-STAD and HPA data were analyzed to explore HOXC12 level. Kaplan-Meier Plotter was used to analyze the relationship between HOXC12 level and the prognosis of gastric cancer patients. The HOXC12 was knocked down or overexpressed by shRNA or overexpression vector to explore its functions. Cell migration/invasion assays and wound healing assay were used to assess the invasion/migration ability of gastric cancer cells. Western blot and qPCR were used to detect gene expression and the activation of Wnt/β-catenin signaling pathway. Dual-luciferase reporter assay was used to detect the active region bound by HOXC12 in the promoter of Spalt-like transcription factor 4 (SALL4). RESULTS: HOXC12 was highly expressed in gastric cancer and was positively correlated with the poor prognosis of gastric cancer patients. HOXC12 promotes the invasion and migration of gastric cancer cells via Wnt/β-catenin signaling pathway. HOXC12 upregulated the transcription of SALL4 by binding to its promoter. HOXC12 was negatively correlated with both the levels of CD8(+) T cells and T cell cytotoxicity-related genes. CONCLUSION: HOXC12 promotes the invasion/migration of gastric cancer cells via SALL4/Wnt/β-catenin axis, and is negatively correlated with the infiltration of CD8(+) T cells, suggesting HOXC12 as a diagnostic marker and a potential therapeutic target for gastric cancer.