WWOX regulates the Elf5/Snail1 pathway to affect epithelial-mesenchymal transition of ovarian carcinoma cells in vitro

摘要

OBJECTIVE: Ovarian cancer is a highly invasive type of cancer. A previous study demonstrated that E-cadherin expression was upregulated in a human ovarian cancer cell line with a high expression of WW domain-containing oxidoreductase (WWOX), which is a tumor suppressor. Also, the migration and invasion ability of these cells was reduced. Snail family members are involved in the epithelial-to-mesenchymal transition (EMT) of ovarian cancer cells, and the expression of Snail family members is regulated by the transcription factor Elf5. The aim of the present research was to elucidate the role of WWOX in EMT of ovarian carcinoma cells through the Elf5/Snail pathway by gain and loss of function approaches in in vitro experiments. MATERIALS AND METHODS: First, a WWOX gene expressing plasmid was transfected into CD133+CD117+ HO8910 ovarian carcinoma cells, and an Elf5 shRNA plasmid was transfected into these cells to assess the changes in EMT-related factors, including Snail1, and the invasive ability of tumor cells ability. Second, the human ovarian carcinoma cell lines HO8910 and SKOV3 were divided into six groups to detect the same indicators. RESULTS: The results demonstrated that the high expression of WWOX resulted in an increased E-cadherin expression, decreased Snail1 activity, and decreased invasion ability in CD133+CD117+ HO8910 cells. Elf5 shRNA transfection did not affect the WWOX expression; however, it decreased the expression of E-cadherin and Elf5 activity, while increasing Snail1 activity and invasion ability in CD133+CD117+ HO8910 cells. It was also observed that WWOX overexpression in HO8910 and SKOV3 cells inhibited the expression of EMT-related proteins and inhibited cell migration and invasion. CONCLUSIONS: Taken together, the results of the present report suggest that WWOX can decrease Snail1 activity by enhancing the activity of Elf5, thus upregulating E-cadherin expression and eventually inhibiting EMT of ovarian carcinoma.