Oncotarget

Research Papers:

Prostate-derived ETS factor improves prognosis and represses proliferation and invasion in hepatocellular carcinoma

Er-Bao Chen, Shao-Lai Zhou, Xu-Guang Pang, Dan Yin, Pei-Zhen Miao, Yi Yang, Qing Chen, Kai Zhu, Dong-Mei Gao, Tian-Shu Liu, Xiao-Yi Wang, Ying-Hong Shi, Wei-Zhong Wu, Jian Zhou, Zheng-Jun Zhou and Zhi Dai _

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Oncotarget. 2017; 8:52488-52500. https://doi.org/10.18632/oncotarget.14924

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Abstract

Er-Bao Chen1,2,*, Shao-Lai Zhou1,*, Xu-Guang Pang3,*, Dan Yin1, Pei-Zhen Miao1, Yi Yang1, Qing Chen1, Kai Zhu1, Dong-Mei Gao1, Tian-Shu Liu4, Xiao-Yi Wang1, Ying-Hong Shi1, Wei-Zhong Wu1, Jian Zhou1,2, Zheng-Jun Zhou1 and Zhi Dai1,2

1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Labolatory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China

2State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China

3Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

4Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China

*These authors have contributed equally to this work

Correspondence to:

Zhi Dai, email: dai.zhi@zs-hospital.sh.cn

Zheng-Jun Zhou, email: zhou.zhengjun@zs-hospital.sh.cn

Keywords: PDEF, HCC, EMT, invasion, proliferation

Received: August 25, 2016     Accepted: December 27, 2016     Published: January 31, 2017

ABSTRACT

Prostate-derived E-twenty-six (ETS) factor (PDEF), an epithelium-specific ETS transcription factor, regulates carcinogenesis and tumor progression. The prognostic importance and biologic functions in hepatocellular carcinoma (HCC) have not been established. We investigated PDEF expression in 400 HCC patients using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry analysis. PDEF expression was significantly lower in tumors than in peritumoral tissues. Lower PDEF levels were associated with poorer prognosis in patients. PDEF was an independent predictor of overall survival in multivariate analysis. PDEF expression was suppressed in highly metastatic HCC cell lines, and shRNA-mediated down-regulation of PDEF in low-metastatic HCC cell lines (with high PDEF) significantly increased cellular proliferative and invasive capacity in vitro and in vivo. RNA sequencing analysis indicated that PDEF may mediate transcription of several genes involved in apoptosis and the cell cycle. PDEF modulated epithelial-mesenchymal transition by up-regulating E-cadherin expression and down-regulating Slug and Vimentin expression, thereby lowering migration and invasion abilities of HCC cells. In conclusion, PDEF is associated with proliferation and invasiveness of HCC cells. It may serve as an independent predictor of prognosis in patients with HCC.


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