Oncotarget

Research Papers:

Ang-2 promotes lung cancer metastasis by increasing epithelial-mesenchymal transition

Zhizhen Dong, Jianrong Chen, Xuli Yang, Wenjie Zheng, Li Wang, Miao Fang, Mengna Wu, Min Yao, Dengfu Yao _

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Oncotarget. 2018; 9:12705-12717. https://doi.org/10.18632/oncotarget.24061

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Abstract

Zhizhen Dong1,*, Jianrong Chen2,*, Xuli Yang1,*, Wenjie Zheng1, Li Wang3, Miao Fang1, Mengna Wu1, Min Yao3 and Dengfu Yao1

1Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China

2Department of Respiratory Medicine, Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China

3Departments of Medical Informatics & Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China

*These authors have contributed equally to this work

Correspondence to:

Dengfu Yao, email: yaodf@ahnmc.com

Min Yao, email: erbei@ntu.edu.cn

Keywords: lung cancer; Ang-2; RNA interference; EMT; prognosis

Received: October 26, 2017    Accepted: January 03, 2018    Published: January 09, 2018

ABSTRACT

Lung cancer is the most common malignant tumor with increasing angiopoietin-2 (Ang-2) and a high rate of metastasis. However, the mechanism of Ang-2 enhancing tumor proliferation and facilitating metastasis remains to be clarified. In this study, Ang-2 expression and its gene transcription on effects of biological behaviors and epithelial-mesenchymal transition (EMT) were investigated in lung cancers. Total incidence of Ang-2 expression in the cancerous tissues was up to 91.8 % (112 of 122) with significantly higher (χ2=103.753, P<0.001) than that in the paracancerous tissues (27.9%, 34 of 122). High Ang-2 expression was closely related to tumor size (χ2=7.883, P=0.005), differentiation degree (χ2=4.554, P=0.033), tumor node metastasis (TNM) staging (χ2=5.039, P=0.025), and 5-year survival rate (χ2 =11.220, P<0.001) with significantly shorter than that of cases with low or no Ang-2. Significant difference was found at TNM staging I (χ2=18.881, P<0.001) and not at II (χ2=0.81, P=0.776) or III & IV (χ2=1.845, P=0.174). Over-expression of Ang-2 or Ang-2 mRNA in lung A549 and NCI-H1975 cells were identified among different cell lines. When silencing Ang-2 in A549 cells with specific shRNA-1 transfection, the cell proliferation was significantly inhibited in a time-dependent manner, with up-regulating E-cadherin, down-regulating Vimentin, Twist, and Snail expression, and decreasing invasion and metastasis of cancer cell abilities, suggesting that Ang-2 promote tumor metastasis through increasing EMT, and it could be a potential target for lung cancer therapy.


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