Oncotarget

Research Papers:

Overexpression of WWP1 promotes tumorigenesis and predicts unfavorable prognosis in patients with hepatocellular carcinoma

Xiao-Fei Zhang _, Jie Chao, Qiu-Zhong Pan, Ke Pan, De-Sheng Weng, Qi-Jing Wang, Jing-Jing Zhao, Jia He, Qing Liu, Shan-Shan Jiang, Chang-Long Chen, Hong-Xia Zhang and Jian-Chuan Xia

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Oncotarget. 2015; 6:40920-40933. https://doi.org/10.18632/oncotarget.5712

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Abstract

Xiao-Fei Zhang1,2,*, Jie Chao3,*, Qiu-Zhong Pan1,2, Ke Pan1,2, De-Sheng Weng1,2, Qi-Jing Wang2, Jing-Jing Zhao1,2, Jia He2, Qing Liu2, Shan-Shan Jiang1,2, Chang-Long Chen1,2, Hong-Xia Zhang1,2, Jian-Chuan Xia1,2

1State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China

3Shanxi Entry-Exit Inspection and Quarantine Bureau, Shanxi 710068, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Jian-Chuan Xia, e-mail: xiajch@mail.sysu.edu.cn

Keywords: WWP1, hepatocellular carcinoma, prognosis, oncogene

Received: August 12, 2015     Accepted: September 16, 2015     Published: October 17, 2015

ABSTRACT

WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) has been speculated to play important roles in the development of several kinds of cancers. However, the role of WWP1 in hepatocellular carcinoma(HCC) is not clear. In the present study, we investigated the expression and prognostic role of WWP1 in primary hepatocellular carcinoma (HCC) using cell lines and 149 archived HCC samples. Correlation between the functions of WWP1 in HCC was also explored. We used human HCC cell lines (BEL-7402, SMMC-7721, Hep-G2, Hep-3B, SK-hep1 and Huh7) and a normal hepatocyte cell line (LO2) along with HCC samples from patients who had undergone resection for HCC previously at our hospital. A battery of methods (real-time quantitative polymerase chain reaction; western blotting; immunohistochemical analyses; cell proliferation and colony formation assays; cell migration and cell invasion assays) were employed to assess various aspects of WWP1. We found that WWP1 expression was upregulated aberrantly at mRNA and protein levels in human primary HCC tissues. Amplified expression of WWP1 was highly correlated with poor outcome. Silencing of WWP1 expression by siRNA inhibited the proliferation, colony formation, migration and invasion of HCC cells in vitro, and resulted in significant apoptosis and cycle arrest in HCC cells. Our findings suggest that WWP1 might have an oncogenic role in human primary HCC, and that it could be used as a prognostic marker as well as a potential molecular target for the treatment of HCC.


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