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Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial–Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer Cells

Wenzhang Zhang*1, Xin Wu†1, Liang Hu*, Yuefan Ma*, Zihan Xiu*, Bingyu Huang*, Yun Feng*, Xudong Tang*†‡

* Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, Guangdong, P.R. China
† Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, P.R. China
‡ Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, P.R. China
1 These authors provided equal contribution to this work.

Oncology Research 2017, 25(5), 843-852. https://doi.org/10.3727/096504016X14813880882288

Abstract

The human papillomavirus (HPV) infection may be associated with the development and progression of nonsmall cell lung cancer (NSCLC). However, the role of HPV-16 oncoproteins in the development and progression of NSCLC is not completely clear. Epithelial–mesenchymal transition (EMT), a crucial step for invasion and metastasis, plays a key role in the development and progression of NSCLC. Here we explored the effect of HPV-16 oncoproteins on EMT and the underlying mechanisms. NSCLC cell lines, A549 and NCI-H460, were transiently transfected with the EGFP-N1-HPV-16 E6 or E7 plasmid. Real-time PCR and Western blot analysis were performed to analyze the expression of EMT markers. A protein microarray was used to screen the involved signaling pathway. Our results showed that overexpression of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted EMT-like morphologic changes, downregulated the mRNA and protein levels of EMT epithelial markers (E-cadherin and ZO-1), and upregulated the mRNA and protein levels of EMT mesenchymal markers (N-cadherin and vimentin) and transcription factors (ZEB-1 and Snail-1). Furthermore, the HPV-16 E6 oncoprotein promoted STAT3 activation. Moreover, WP1066, a specific signal transducer and activator of transcription 3 (STAT3) inhibitor, reversed the effect of HPV-16 E6 on the expression of ZO-1, vimentin, and ZEB-1 in transfected NSCLC cells. Taken together, our results suggest that overexpression of HPV-16 E6 and E7 oncoproteins enhances EMT, and the STAT3 signaling pathway may be involved in HPV-16 E6-induced EMT in NSCLC cells.

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APA Style
Zhang, W., Wu, X., Hu, L., Ma, Y., Xiu, Z. et al. (2017). Overexpression of human papillomavirus type 16 oncoproteins enhances epithelial–mesenchymal transition via STAT3 signaling pathway in non-small cell lung cancer cells. Oncology Research, 25(5), 843-852. https://doi.org/10.3727/096504016X14813880882288
Vancouver Style
Zhang W, Wu X, Hu L, Ma Y, Xiu Z, Huang B, et al. Overexpression of human papillomavirus type 16 oncoproteins enhances epithelial–mesenchymal transition via STAT3 signaling pathway in non-small cell lung cancer cells. Oncol Res. 2017;25(5):843-852 https://doi.org/10.3727/096504016X14813880882288
IEEE Style
W. Zhang et al., "Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial–Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer Cells," Oncol. Res., vol. 25, no. 5, pp. 843-852. 2017. https://doi.org/10.3727/096504016X14813880882288



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