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Effect of WWOX on epithelial-mesenchymal transition in ovarian cancer cells <i>in vivo</i>, and its association with Elf5/Snail-1 signal pathway


Chunhuan Song
Yuchen Yan
Yongli Liu
Lisha Fang
Qiang Li
Yang Xu
Hongchao Yan

Abstract

Purpose: To investigate how WW domain-containing oxidoreductase (WWOX) gene affects epithelial-mesenchymal transition (EMT) of ovarian cancer (OC) cells, and the implication of Elf5/Snail-1 pathway in the process.


Methods: This study employed female BALB/c nude mice aged 6 weeks. The expression levels of E-cadherin, β-Catenin, N-cadherin, Vimentin, Snail1 and Elf5 were assayed using qRT-PCR. The protein levels of WW1, WW2, E-cad, β-Cat, N-cad, vimentin, Snail-1 and Elf5 were determined using western blotting (WB). Invasion changes in cells in each group were analyzed by Transwell invasion test while WWOX and Elf5 were evaluated by GST pull-down test; furthermore, WWOX and ELF5 were evaluated by co-immunoprecipitation (COIP).


Results: Relative to control group, tumor volume and weight of WWOX high-expression mice were significantly decreased, while those of WWOX low-expression group were increased (p < 0.05). The levels of E-cad, Elf5 and β-catenin increased, but those of N-cad, Snail-1 and vimentin decreased in WWOX high expression group. In the WWOX low-expression group, the levels of E-cad, Elf5 and β-cat were down-regulated, while those of N-cad, Snail-1 and vimentin were up-regulated (p < 0.05). The expression of E-cad, Elf5 and β-cat declined; on the other hand, those of N-Cad, Snail-1 and vimentin were elevated after mutation of WW1 domain in WWOX gene (p < 0.05).


Conclusion: Based on the in vivo results, the role of WWOX/Elf5/Snail1 signal route in the epithelial-mesenchymal transition of ovarian cancer, and its related mechanisms have been clarified. This provides a new target for gene therapy of ovarian cancer.


Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996