Abstract
Purpose
To evaluate the expression levels of spalt-like transcription factor 4 (SALL4) in bladder urothelial carcinoma, and determine its role and underlying mechanism of action in mediating the proliferation, migration and invasion of bladder cancer cells.
Methods
SALL4 expression was examined in 170 bladder patient urothelial carcinoma tissue samples by immunohistochemistry. Using a SALL4 overexpression plasmid and siRNA-SALL4, the effects of overexpressing and silencing SALL4 on the proliferation, migration and invasion of T24 and 5637 bladder cancer cells was examined using CCK8, migration and invasion assays. Western blot analysis was performed to detect epithelial mesenchymal transition (EMT)-related protein expression.
Results
The expression rate of SALL4 in low-grade and high-grade urothelial carcinomas was found to be 10% and 49.12%, respectively (P < 0.001), while SALL4 expression was not observed in the normal urothelium. SALL4 protein expression was positively correlated with histological grade, depth of invasion, lymphatic metastasis and vascular invasion of bladder urothelial carcinoma (P < 0.05). In addition, a shorter overall survival time and poor prognosis was observed in the SALL4 protein expression group. Overexpression of SALL4 led to significantly increased cell proliferation, migration and invasion, while knockdown of SALL4 had the opposite effect. In the SALL4 overexpression group, N-cadherin, vimentin, Snail and β-catenin expression were significantly increased, while E-cadherin expression was significantly decreased (P < 0.05). Promotion of EMT was also observed in SALL4-overexpressing cells. In contrast, in the SALL4-siRNA-treated group, EMT was reversed and β-catenin expression was reduced.
Conclusions
Our data show that the SALL4 gene is associated with the proliferation, invasion and poor prognosis of bladder urothelial carcinoma, and may mediate its effects via the Wnt/β-catenin signaling pathway, which regulates the EMT pathway. Thus, down-regulation of SALL4 may provide a novel therapeutic strategy for the treatment of bladder urothelial carcinoma.