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GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process

Authors Shen J, Lv X, Zhang L

Received 18 November 2019

Accepted for publication 13 February 2020

Published 25 March 2020 Volume 2020:13 Pages 2511—2522

DOI https://doi.org/10.2147/OTT.S239120

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Gaetano Romano


Jingang Shen,1,* Xianbao Lv,1,* Lei Zhang2

1Department of Urology, Chengwu County People’s Hospital, Shandong 274200, People’s Republic of China; 2Department of Urology, Zoucheng People’s Hospital, Shandong 273500, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lei Zhang
Department of Urology, Zoucheng People’s Hospital, No. 59, Qianquan Road, Zoucheng County, Jining, Shandong 273500, People’s Republic of China
Tel +86-13506385177
Email qifeng2001oy@163.com

Purpose: GRHL2 played important roles in different cancers. In this study, we aimed to investigate the roles of GRHL2 in bladder cancer.
Methods: The immunohistochemistry assay was performed to detect the expression of GRHL2 in bladder cancer tissues and adjacent noncancerous tissues and the expression levels of GRHL2 and zinc finger E-box binding homeobox (ZEB1) mRNA in tissues were determined by qRT-PCR. In addition, qRT-PCR and Western blotting were applied to detect the expression levels of GRHL2 and ZEB1 in bladder cancer cell lines (RT4, BIU-87, 5637, T24) and immortalized human bladder epithelial cell line (SV-HUC-1). The cell models with up-regulated and down-regulated expression of GRHL2 were constructed using bladder cancer cell lines T24 and 5637 to investigate the underlying roles of GRHL2 on the proliferation, migration, invasion and EMT process of bladder cancer cells. After that, cell proliferation was evaluated by CCK8 assay, cell cycle assay and colony formation assay. Transwell assay and wound healing assay were performed to determine the invasion and migration ability of the bladder cancer cells. The expressions of epithelial-mesenchymal transition (EMT) related proteins (E-cadherin, Vimentin, Slug and Snail) were assessed by Western blot analysis. Moreover, ZEB1 and GRHL2 were co-transfected into T24 and 5637 cells and their effects on EMT process and invasive capacity of cells were examined.
Results: The expression of GRHL2 was down-regulated in bladder cancer tissues and human bladder cancer cell lines compared with the normal bladder tissues and immortalized human bladder epithelial cell line. Besides, down-regulation of GRHL2 improved the proliferation ability of bladder cancer cells and promoted the EMT process through up-regulation of ZEB1. The overexpression of ZEB1 partially reversed the inhibitory effect of GRHL2 on EMT.
Conclusion: GRHL2 acts as an anti-oncogene to regulate bladder cancer cell proliferation and inhibit EMT by targeting ZEB1. This study may provide a theoretical basis for further research.

Keywords: bladder cancer, GRHL2, EMT, ZEB1

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