ΔNp63α attenuates tumor aggressiveness by suppressing miR-205/ZEB1-mediated epithelial-mesenchymal transition in cervical squamous cell carcinoma

Cervical cancer is one of the most common female cancers worldwide. Although the therapeutic outcomes of patients with early-stage cervical cancer have been significantly improved in the past decades, tumor metastasis and recurrence remain the major causes of cervical cancer-related deaths. In cervical squamous cell carcinoma (SCC), the aberrant activation of epithelial-mesenchymal transition (EMT), a crucial process in invasion and metastasis of epithelial cancer, could promote lymph nodal metastasis and recurrence, and predicts poor prognosis. In this study, we show that the expression levels of EMT markers, beta-catenin and Vimentin, are associated with the p63 isoform Delta Np63 alpha in SCC by using immunohistochemistry staining and analysis. Compared to the control SiHa cells (SiHa-NC), the expression of E-cadherin and beta-catenin are upregulated, while Vimentin and ZEB1 are downregulated in the constructed SiHa cell line with stable Delta Np63 alpha overexpression (SiHa-Delta Np63 alpha). Besides, the migration and invasion abilities are also suppressed in SiHa-Delta Np63 alpha cells with a typical epithelial morphology with cobblestone-like shape, suggesting that Delta Np63 alpha is a vital EMT repressor in SCC cells. In addition, the involvement of miR-205/ZEB1 axis in the inhibition effect of Delta Np63 alpha on EMT program is revealed by a miRNA array and confirmed by the subsequent transfection of the miR-205 mimic and antagomir. Moreover, SCC patients with low Delta Np63 alpha expression and high EMT level show more frequent metastasis and recurrence as well as reduced overall survival. Therefore, EMT program and its vital repressor Delta Np63 alpha could be used as biomarkers for tumor metastasis and recurrence in cervical cancer.