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Effect of YAP1 silencing on esophageal cancer

Authors Zhao J, Li X, Yang Y, Zhu D, Zhang C, Liu D, Wu K, Zhao S

Received 11 December 2015

Accepted for publication 16 March 2016

Published 26 May 2016 Volume 2016:9 Pages 3137—3146

DOI https://doi.org/10.2147/OTT.S102338

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 4

Editor who approved publication: Dr Faris Farassati


Jia Zhao,1,2 Xiangnan Li,1,2 Yang Yang,1,2 Dengyan Zhu,1,2 Chunyang Zhang,1,2 Donglei Liu,1,2 Kai Wu,1,2 Song Zhao1,2

1Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, 2Key Thoracic Tumour Experimental Laboratory of Zhengzhou, Zhengzhou, Henan, People’s Republic of China

Background: YAP1, the nuclear effector of the Hippo pathway, has become an attractive target for treatment of malignancies and is a candidate oncogene in esophageal cancer (EC). We hypothesized that knockdown of YAP1 could suppress EC and could be used for targeted therapy. However, there are few reports of the effect of YAP1 knockdown in EC.
Materials and methods: Quantitative real-time polymerase chain reaction and Western blot assays were performed to determine the expression levels of YAP1 mRNA and protein in primary EC tissue samples, EC cell lines, and controls. Immunohistochemistry was also performed to detect YAP1 protein expression in primary EC tumor and matched nontumor control tissues. YAP1-knockdown cell lines were constructed using short-hairpin RNA, and MTT, flow cytometry, and transwell chamber assays were used to analyze the effect of YAP1 knockdown on EC cell proliferation, apoptosis, and invasion. In vivo tumor formation assays were used to investigate the antitumor effect of YAP1 knockdown.
Results:
We found that YAP1 mRNA and protein were upregulated in EC and that YAP1 expression correlated significantly with metastasis and tumor stage. We also found that YAP1 knockdown repressed cell proliferation and invasion and promoted apoptosis of EC cell lines. In addition, animal experiments revealed that YAP1 knockdown suppressed the growth of esophageal tumors in vivo.
Conclusion:
Collectively, these data confirm our hypothesis that YAP1 knockdown suppresses EC and suggest that YAP1 knockdown could be exploited in the targeted gene therapy of EC in the future.

Keywords: esophageal cancer, Hippo, YAP1 knockdown, animal experiments

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