KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression

Abstract KDM6B (Lysine-specific demethylase 6B) is a histone lysine demethyltransferase that plays a key role in many types of cancers. However, its potential role in gastric cancer (GC) remains unclear. Here, we focused on the clinical significance and potential role of KDM6B in GC. We found that the KDM6B expression is upregulated in GC tissues and that its high expression in patients is related to poor prognosis. KDM6B ectopic expression promotes GC cells’ proliferation and metastasis, while its inhibition has opposite effects in vitro and in vivo. Mechanistically, KDM6B promotes GC cells proliferation and metastasis through its enzymatic activity through the induction of H3K27me3 demethylation near the CXCR4 (C-X-C chemokine receptor type 4) promoter region, resulting in the upregulation of CXCR4 expression. Furthermore, H. pylori was found to induce KDM6B expression. In conclusion, our results suggest that KDM6B is aberrantly expressed in GC and plays a key role in gastric carcinogenesis and metastasis through CXCR4 upregulation. Our work also suggests that KDM6B may be a potential oncogenic factor and a therapeutic target for GC.