Downregulated KDM6A mediates gastric carcinogenesis via Wnt/β-catenin signaling pathway mediated epithelial-to-mesenchymal transition

This study explored the connection between KDM6A expression and patient prognosis and the mechanism of KDM6A's role in developing GC (GC). From the immunohistochemical Analysis of 107 GC patients' tumors, we discovered that patients with reduced KDM6A expression had a shorter survival time. There was a correlation between KDM6A expression and the degree of differentiation of tumor tissue, T stage, N stage, and TNM stage. KDM6A gene expression was positively connected with the expression level of E-cadherin and negatively connected with the expression level of N-cadherin and vimentin in vitro tests. KDM6A gene suppression prevented GC cell proliferation, migration, and invasion, whereas high KDM6A gene expression promoted these processes. Second, low expression of KDM6A down-regulates GSK3 beta, p-GSK3 beta, up-regulates C-Myc, CyclinD1, and promotes beta-catenin protein expression in the nucleus, while the high expression does the opposite. Then, we used ICG001 to block the Wnt/beta-catenin signal transduction pathway, and the results revealed that ICG001 could reduce the promoting effect of low KDM6A expression on aggressiveness and EMT in GC cells. KDM6A down-regulation stimulates the proliferation of GC cells, while ICG001 reverses this action in vivo tests. Patients whose KDM6A expression was found to be low had a poor prognosis, as this study found. The EMT is inhibited by regulating theWnt/beta-catenin signaling by KDM6A, which reduces GC cell proliferation, migration, and invasion. KDM6A may be a viable target for GC in clinical therapy.