title: ΔNp63α attenuates tumor aggressiveness by suppressing miR-205/ZEB1-mediated epithelial-mesenchymal transition in cervical squamous cell carcinoma.
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.
authors: Department of Obstetrics and Gynecology, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, China. victorzhao@163.com.|Department of Gynecologic Oncology, Anhui Provincial Cancer Hospital, Hefei, China. victorzhao@163.com.|Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China. victorzhao@163.com.
authors: Weidong
authors: W
authors: Zhao
authors: Department of Gynecologic Oncology, Anhui Provincial Cancer Hospital, Hefei, China.
authors: Huiyan
authors: H
authors: Wang
authors: Department of Obstetrics and Gynecology, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, China.
authors: Xiaohui
authors: X
authors: Han
authors: Department of Gynecologic Oncology, Anhui Provincial Cancer Hospital, Hefei, China.
authors: Jie
authors: J
authors: Ma
authors: Department of Gynecologic Oncology, Anhui Provincial Cancer Hospital, Hefei, China.
authors: Yuanyuan
authors: Y
authors: Zhou
authors: Department of Obstetrics and Gynecology, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, China.
authors: Zhengzheng
authors: Z
authors: Chen
authors: Department of Gynecologic Oncology, Anhui Provincial Cancer Hospital, Hefei, China.
authors: Hu
authors: H
authors: Zhou
authors: Department of Obstetrics and Gynecology, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, China.
authors: Hanjie
authors: H
authors: Xu
authors: Department of Obstetrics and Gynecology, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, China.
authors: Zhengwei
authors: Z
authors: Sun
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
authors: Beihua
authors: B
authors: Kong
authors: Department of Nursing, Anhui Vocational Institute of Population, Chizhou, China.
authors: Huiying
authors: H
authors: Fang
mesh_terms: D000328:Adult; D000070416:Antagomirs / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D020033:Protein Isoforms / Q000502:physiology; D012334:RNA, Neoplasm / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000502:physiology*; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000070416:Antagomirs; D035683:MicroRNAs; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014746:Vimentin; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin; C495270:CTNNB1 protein, human; C534425:MIR205, human; C115051:TP63 protein, human; C486307:ZEB1 protein, human
keywords: Cervical squamous cell carcinoma; Epithelial–mesenchymal transition; Vimentin; ΔNp63α; β-catenin