KDM4B promotes gastric cancer metastasis by regulating miR‐125b‐mediated activation of Wnt signaling

Emerging evidence has demonstrated that the aberrant expression of histone‐modifying enzymes such as histone demethylases contributes to gastric carcinogenesis and progression. The role of KDM4B in cancer progression has been gradually revealed. However, the underlying mechanisms regulating gastric cancer metastasis of KDM4B remain unclear. In the present study we determined KDM4B expression in gastric cancer and its biologic function in vitro and in vivo. We found that KDM4B expression was significantly increased in most gastric cancer tissues compared with the adjacent normal tissues. Upregulated expression of KDM4B in human gastric cancer was correlated with poor prognosis. In vitro, KDM4B overexpression in AGS cells promoted cell invasion, whereas knockdown of KDM4B inhibited cell invasion. Furthermore, KDM4B overexpression also promoted tumor metastasis in vivo. Mechanistically, KDM4B upregulated miR‐125b expression and activated Wnt signaling pathway. More important, miR‐125b partially mediated KDM4B‐induced activation of Wnt signaling. Finally, we demonstrated that KDM4B promoted gastric cancer cell invasion in vitro and cancer metastasis in vivo, at least in part, by upregulating miR‐125b expression. These data provided novel insights on the role of KDM4B‐driven gastric cancer metastasis and indicated that KDM4B may be served as a potential target for gastric cancer. KDM4B promotes gastric cancer metastasis by regulating miR‐125b‐mediated activation of Wnt signaling. These data provided novel insights on the role of KDM4B‐driven gastric cancer metastasis and indicated that KDM4B may be served as a potential target for gastric cancer.