Abstract
Over the last few decades, predictive markers for the prognosis of gastric cancer have not been extensively investigated. The present study aimed to evaluate the expression profile of histone demethylase lysine (K)-specific demethylase 6B (KDM6B) in gastric cancer and healthy control tissues, as well as its value in prognosis prediction as a clinical marker. Within the framework of these criteria, the diagnostic role of KMD6B for gastric cancer was investigated, which may provide insights into novel treatment targets. Immunohistochemistry was applied to detect KMD6B expression in 100 gastric cancer tissues and matching para-cancerous tissues to analyze the association between KMD6B expression and clinicopathological features. Based on the follow-up data, the value of KMD6B in prognosis assessment was further explored. The role of KMD6B in gastric cancer cell proliferation, cell cycle distribution and the expression of cell cycle-associated proteins was investigated by inhibiting KMD6B activity using the specific inhibitor GSK J4. KMD6B was mostly distributed in cytoplasm and nucleus in gastric cancer tissue. The expression level was significantly higher in cancer tissues compared with that in the corresponding non-cancerous tissues. The expression of KMD6B was significantly associated with sex, lymph node and distant metastasis status and clinical stage (P<0.05). Cell proliferation was significantly decreased with the inhibition of KMD6B activity, and the cell cycle in HGC27 cells was arrested in the G2/M phase after being treated with GSK J4 for 24 h. The expression of cyclin B and Cdc2 were significantly decreased, while p21 was upregulated. It was concluded that the dysregulated expression of KMD6B is associated with the malignant progression of gastric cancer and could be a potential marker for prognosis. Blocking the demethylase activity of KMD6B induced G2/M arrest and inhibited the proliferation of gastric cancer cells, suggesting that KMD6B is a potential novel therapeutic target for gastric cancer.