JWA deficiency induces malignant transformation of murine embryonic fibroblast cells.

The present study aimed to investigate the effects of JWA knockout (JWA) on malignant transformation of murine embryonic fibroblast (MEF) cells using a conditional JWA mouse model. Once MEF cells were prepared, the potential role of JWA on proliferation, migration, invasion and colony formation of MEF cells was investigated by cytological examination. The effects of JWA on the regulation and protein expression levels of epithelial-mesenchymal transition (EMT)-related proteins in MEF cells, including poly(ADP-ribose) polymerase-1 (PARP-1), vimentin, β-catenin and E-cadherin, were investigated using western blot analysis. The tumorigenicity of JWA deficiency was explored using nude mouse xenografts and subcutaneous inoculation of MEF cells exhibiting JWA. JWA was able to increase cell proliferation, migration, invasion and colony formation in the malignant transformation of MEF cells. The protein expression levels of PARP-1, vimentin and β-catenin were upregulated, whereas E-cadherin was downregulated in JWA MEF cells. The tumor formation was observed in mice following subcutaneous inoculation of MEF with JWA, whereas no tumor was formed in the mice treated with functional JWA MEF cells. In conclusion, the present findings suggest that JWA has important roles in cell proliferation, migration, invasion and colony formation and is able to induce the malignant transformation of MEF cells. The expression levels of EMT-related proteins changed and tumorigenicity increased in JWA MEF cells compared with cells with functional JWA. The present findings indicate that JWA may function as an anti-oncogene in tumorigenesis.