Oncotarget

Research Papers:

RMP promotes epithelial-mesenchymal transition through NF-κB/CSN2/Snail pathway in hepatocellular carcinoma

Wei Zhou, Qi Wang, Yi Xu, Jingting Jiang, Jingchun Guo, Huijun Yu and Wenxiang Wei _

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Oncotarget. 2017; 8:40373-40388. https://doi.org/10.18632/oncotarget.16177

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Abstract

Wei Zhou1,*, Qi Wang2,*, Yi Xu1, Jingting Jiang2, Jingchun Guo3, Huijun Yu1 and Wenxiang Wei1

1Department of Cell Biology, Institute of Bioengineering, School of Medicine, Soochow University, Suzhou 215123, China

2Department of Tumor Biotherapy, Third Affiliated Hospital of Soochow University, Changzhou 213003, China

3State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China

*These authors have contributed equally

Correspondence to:

Wenxiang Wei, email: wenxiangw@suda.edu.cn

Huijun Yu, email: hjyu@suda.edu.cn

Keywords: RMP, EMT, HCC, NF-κB, metastasis

Received: September 06, 2016    Accepted: February 20, 2017    Published: March 14, 2017

ABSTRACT

Epithelial-mesenchymal transition (EMT) is a significant risk factor for metastasis in hepatocellular carcinoma (HCC) patients and with poor prognosis. In this study, we demonstrate the key role of RPB5-mediating protein (RMP) in EMT of HCC cells and the mechanism by which RMP promote EMT. RMP increases migration, invasion, and the progress of EMT of HCC cells, which facilitates the accumulation of Snail, a transcriptional repressor involved in EMT initiation. NF-κB is activated by RMP, which directly promotes the expression of COP9 signalosome 2 (CSN2) to repress the degradation of Snail. Pulmonary metastases mouse model demonstrates that RMP induces metastasis in vivo. Immunohistochemical analysis of human HCC tissues confirms the correlation of RMP with the expression of E-cadherin, p65, CSN2 and Snail in vivo. Collectively, these findings indicate that RMP promotes EMT and HCC metastasis through NF-κB/CSN2/Snail pathway. These results suggest that RMP and p65 may serve as potential candidates of the targets in the treatment of metastatic HCC.


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