Effect of YAP1 silencing on esophageal cancer
Jia Zhao1, Xiangnan Li1, Yang Yang1
1Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Key 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.
Insights
YAP1 (Yes-associated protein 1) knockdown suppresses esophageal cancer (EC) by inhibiting proliferation and invasion while promoting apoptosis. This study confirms YAP1 as a therapeutic target for EC gene therapy.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Yes-associated protein 1 (YAP1) is a key effector of the Hippo pathway and a potential oncogene in esophageal cancer (EC).
- Limited research exists on the impact of YAP1 knockdown in EC.
- YAP1's role in malignancies makes it an attractive therapeutic target.
Purpose of the Study:
- To investigate the effect of YAP1 knockdown on esophageal cancer.
- To evaluate YAP1 as a potential therapeutic target for EC.
Main Methods:
- Quantitative real-time polymerase chain reaction and Western blot assays to measure YAP1 expression.
- Immunohistochemistry to detect YAP1 protein in tumor tissues.
- YAP1-knockdown cell lines generated using short-hairpin RNA.
- MTT, flow cytometry, transwell, and in vivo tumor formation assays to assess cellular behavior and tumor growth.
Main Results:
- YAP1 mRNA and protein levels were significantly upregulated in EC tissues and correlated with tumor stage and metastasis.
- YAP1 knockdown suppressed EC cell proliferation and invasion.
- YAP1 knockdown induced apoptosis in EC cell lines.
- In vivo studies demonstrated that YAP1 knockdown inhibited esophageal tumor growth.
Conclusions:
- YAP1 knockdown effectively suppresses esophageal cancer progression.
- YAP1 represents a promising target for future EC gene-targeted therapy.
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