Graduate School of Xuzhou Medical University, Xuzhou, P.R. China.
Eur Rev Med Pharmacol Sci. 2020 Feb;24(3):1041-1053. doi: 10.26355/eurrev_202002_20154.
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.
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.
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.
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.
卵巢癌是一种侵袭性很强的癌症。先前的研究表明，在 WW 结构域氧化还原酶（WWOX）高表达的人卵巢癌细胞系中，E-钙黏蛋白表达上调，而 WWOX 是一种肿瘤抑制因子。此外，这些细胞的迁移和侵袭能力降低。Snail 家族成员参与卵巢癌细胞的上皮间质转化（EMT），Snail 家族成员的表达受转录因子 Elf5 调节。本研究旨在通过体外实验中的 gain 和 loss of function 方法，阐明 WWOX 通过 Elf5/Snail 通路在卵巢癌细胞 EMT 中的作用。
首先，将 WWOX 基因表达质粒转染到 CD133+CD117+HO8910 卵巢癌细胞中，并将 Elf5 shRNA 质粒转染到这些细胞中，以评估 EMT 相关因子的变化，包括 Snail1 和肿瘤细胞侵袭能力。其次，将人卵巢癌细胞系 HO8910 和 SKOV3 分为六组检测相同指标。
结果表明，WWOX 的高表达导致 CD133+CD117+HO8910 细胞中 E-钙黏蛋白表达增加，Snail1 活性降低，侵袭能力降低。Elf5 shRNA 转染不影响 WWOX 表达；然而，它降低了 E-钙黏蛋白的表达和 Elf5 活性，同时增加了 CD133+CD117+HO8910 细胞中 Snail1 活性和侵袭能力。还观察到，HO8910 和 SKOV3 细胞中 WWOX 的过表达抑制了 EMT 相关蛋白的表达，并抑制了细胞迁移和侵袭。
综上所述，本研究结果表明，WWOX 通过增强 Elf5 的活性降低 Snail1 活性，从而上调 E-钙黏蛋白的表达，最终抑制卵巢癌的 EMT。
