SPAG9 promotes endometrial carcinoma cell invasion through regulation of genes related to the epithelial-mesenchymal transition.

Abstract

To investigate the impact of sperm-associated antigen 9 (SPAG9) on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in endometrial cancer. The present authors' previous study demonstrated that SPAG9 is highly expressed in endometrial cancer tissues. They analyzed correlation between the levels of SPAG9 and mRNA of EMT-related genes in endometrial carcinoma tissue by using quantitative real-time PCR. They induced EMT process in ECC endometrial cancer cell lines by TGF-beta1 treatment and spheroids formation assay, and analyzed SPAG9 expression as well as correlation with EMT-related genes. In addition, they performed SPAG9 gene silencing in KLE and ECC endometrial cancer cells and evaluated the expression of genes involved in EMT, using real time PCR and Western blot analysis. Cell proliferation, colony formation, and transwell assays were employed to evaluate the functional role of SPAG9 in endometrial cancer. The results showed that SPAG9 expression was positively correlated with Slug and N-cadherin (NcaD) in human endometrial cancer tissues. The expression of SPAG9 in ECC cells with TGF-β1 treatment and spheroids formation was increased, which was correlated with EMT-related genes. SPAG9 knockdown significantly inhibited cell growth and proliferation and reduced the motility and invasion of endometrial cancer cells. These phenotypes may partly be explained by decreased expression of EMT-related genes, including Twist, Slug, and Vimentin, after SPAG9 depletion. SPAG9 may be required for cellular invasion and migration in endometrial cancer through regulation of EMT-related genes.