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

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 cont...

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Main Authors: Shen J, Lv X, Zhang L
Format: Article
Language:English
Published: Dove Medical Press 2020-03-01
Series:OncoTargets and Therapy
Subjects:
emt
Online Access:https://www.dovepress.com/grhl2-acts-as-an-anti-oncogene-in-bladder-cancer-by-regulating-zeb1-in-peer-reviewed-article-OTT
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spelling doaj-aae3abce41924f3db3583b02fdf8b0102020-11-25T03:03:26ZengDove Medical PressOncoTargets and Therapy1178-69302020-03-01Volume 132511252252711GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) ProcessShen JLv XZhang LJingang 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 workCorrespondence: Lei ZhangDepartment of Urology, Zoucheng People’s Hospital, No. 59, Qianquan Road, Zoucheng County, Jining, Shandong 273500, People’s Republic of ChinaTel +86-13506385177Email qifeng2001oy@163.comPurpose: 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, ZEB1https://www.dovepress.com/grhl2-acts-as-an-anti-oncogene-in-bladder-cancer-by-regulating-zeb1-in-peer-reviewed-article-OTTbladder cancergrhl2emtzeb1
collection DOAJ
language English
format Article
sources DOAJ
author Shen J
Lv X
Zhang L
spellingShingle Shen J
Lv X
Zhang L
GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process
OncoTargets and Therapy
bladder cancer
grhl2
emt
zeb1
author_facet Shen J
Lv X
Zhang L
author_sort Shen J
title GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process
title_short GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process
title_full GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process
title_fullStr GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process
title_full_unstemmed GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process
title_sort grhl2 acts as an anti-oncogene in bladder cancer by regulating zeb1 in epithelial-mesenchymal transition (emt) process
publisher Dove Medical Press
series OncoTargets and Therapy
issn 1178-6930
publishDate 2020-03-01
description 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 workCorrespondence: Lei ZhangDepartment of Urology, Zoucheng People’s Hospital, No. 59, Qianquan Road, Zoucheng County, Jining, Shandong 273500, People’s Republic of ChinaTel +86-13506385177Email qifeng2001oy@163.comPurpose: 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
topic bladder cancer
grhl2
emt
zeb1
url https://www.dovepress.com/grhl2-acts-as-an-anti-oncogene-in-bladder-cancer-by-regulating-zeb1-in-peer-reviewed-article-OTT
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