Oncotarget

Research Papers:

Oncogenic secretory clusterin in hepatocellular carcinoma: Expression at early staging and emerging molecular target

Wenjie Zheng, Min Yao, Qi Qian, Wenli Sai, Liwei Qiu, Junling Yang, Wei Wu, Zhizhen Dong and Dengfu Yao _

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Oncotarget. 2017; 8:52321-52332. https://doi.org/10.18632/oncotarget.13674

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Abstract

Wenjie Zheng1,*, Min Yao2,*, Qi Qian3,*, Wenli Sai1, Liwei Qiu1, Junling Yang1, Wei Wu1, Zhizhen Dong1,4 and Dengfu Yao1

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

2Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China

3Department of Oncology, Yancheng 1st People’s Hospital, Yancheng 224005, Jiangsu Province, China

4Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China

*These authors have contributed equally to this work

Correspondence to:

Dengfu Yao, email: yaodf@ahnmc.com

Zhizhen Dong, email: dongzz@ahnmc.com

Keywords: hepatocellular carcinoma, secretory clusterin, prognosis, tumor stage, tumor growth

Received: September 20, 2016     Accepted: November 18, 2016     Published: November 29, 2016

ABSTRACT

Secretory clusterin (sCLU) is associated with hepatocellular carcinoma (HCC) progression by contributing to angiogenesis, chemoresistance, cell survival, and metastasis. However, the sCLU expression at early stage of HCC progression remains to be clarified. In this study, the alteration of sCLU oncogenicity was firstly evaluated in HCC- and their para-cancerous- tissues. The incidence of sCLU expression in HCC was significantly higher than that in their non-tumorous tissues at message RNA (mRNA) or protein level, gradually increasing with tumor-node-metastasis (TNM) staging. Abnormal sCLU expression was associated with the poor differentiation, TNM stage, and considered as an independent prognostic factor for HCC patients. Furthermore, silencing sCLU gene transcription inhibited the colony formation and proliferation of HCC cells, with decreasing phosphorylation level of AKT and GSK-3β in HCCLM3 cells in vitro and significantly suppressed the HCC xenograft growth in vivo, suggesting that sCLU with oncogenicity should be not only an early indicator but also novel potential molecular-targeted therapy for HCC.


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