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

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Tumor Biology

Abstract

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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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Acknowledgments

This work was supported by the Key Project of Anhui Provincial University Natural Science Research Foundation from Education Agency of Anhui Province, China (KJ2015A375).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, China

    Weidong Zhao, Xiaohui Han, Zhengzheng Chen, Hanjie Xu & Zhengwei Sun

  2. Department of Gynecologic Oncology, Anhui Provincial Cancer Hospital, Hefei, China

    Weidong Zhao, Huiyan Wang, Jie Ma, Yuanyuan Zhou & Hu Zhou

  3. Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China

    Weidong Zhao & Beihua Kong

  4. Department of Nursing, Anhui Vocational Institute of Population, Chizhou, China

    Huiying Fang

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  1. Weidong Zhao
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Correspondence to Weidong Zhao.

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Zhao, W., Wang, H., Han, X. et al. ΔNp63α attenuates tumor aggressiveness by suppressing miR-205/ZEB1-mediated epithelial–mesenchymal transition in cervical squamous cell carcinoma. Tumor Biol. 37, 10621–10632 (2016). https://doi.org/10.1007/s13277-016-4921-5

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