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Tumor Biology
Published in: Tumor Biology 8/2016

01-08-2016 | Original Article

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

Authors: Weidong Zhao, Huiyan Wang, Xiaohui Han, Jie Ma, Yuanyuan Zhou, Zhengzheng Chen, Hu Zhou, Hanjie Xu, Zhengwei Sun, Beihua Kong, Huiying Fang

Published in: Tumor Biology | Issue 8/2016

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Abstract

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, β-catenin and Vimentin, are associated with the p63 isoform ΔNp63α in SCC by using immunohistochemistry staining and analysis. Compared to the control SiHa cells (SiHa-NC), the expression of E-cadherin and β-catenin are upregulated, while Vimentin and ZEB1 are downregulated in the constructed SiHa cell line with stable ΔNp63α overexpression (SiHa-ΔNp63α). Besides, the migration and invasion abilities are also suppressed in SiHa-ΔNp63α cells with a typical epithelial morphology with cobblestone-like shape, suggesting that ΔNp63α is a vital EMT repressor in SCC cells. In addition, the involvement of miR-205/ZEB1 axis in the inhibition effect of ΔNp63α 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 ΔNp63α expression and high EMT level show more frequent metastasis and recurrence as well as reduced overall survival. Therefore, EMT program and its vital repressor ΔNp63α could be used as biomarkers for tumor metastasis and recurrence in cervical cancer.
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Metadata
Title
ΔNp63α attenuates tumor aggressiveness by suppressing miR-205/ZEB1-mediated epithelial–mesenchymal transition in cervical squamous cell carcinoma
Authors
Weidong Zhao
Huiyan Wang
Xiaohui Han
Jie Ma
Yuanyuan Zhou
Zhengzheng Chen
Hu Zhou
Hanjie Xu
Zhengwei Sun
Beihua Kong
Huiying Fang
Publication date
01-08-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 8/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-4921-5

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