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Epithelial-Mesenchymal Transition Induced by Hepatitis C Virus Core Protein in Cholangiocarcinoma

  • Translational Research and Biomarkers
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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Cholangiocarcinoma (CC) is associated with chronic hepatitis C virus (HCV) infection. We investigated the effect of hepatitis C virus core protein (HCVc) on epithelial-mesenchymal transition (EMT) in CC and tried to identify its target trigger.

Methods

First, we examined expression of HCVc and epithelial and mesenchymal markers in CC tissues. Then we transient-transfected HCVc gene into a CC cell line and examined expression of lysyl oxidase-like 2 (LOXL2) and epithelial and mesenchymal markers by quantitative real-time polymerase chain reaction (PCR) and Western blotting. Finally, LOXL2 gene silencing was shown in QBC939/HCVc cells by RNA interference (RNAi), and we further examined expression of epithelial and mesenchymal markers by quantitative real-time PCR and Western blotting.

Results

Through immunohistochemical staining, the present study showed that HCVc is significantly associated with CC invasion and metastasis. In vitro study showed that HCVc expression induces EMT in CC cell line QBC939, and a mechanism through LOXL2 pathway is suggested. Expression of HCVc was significantly correlated with greater migratory and invasive potential of CC cells.

Conclusions

These observations indicate that HCVc plays a critical role in promoting invasion and metastasis of CC cells.

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Acknowledgment

We acknowledge grant (30872496) from National Nature Science Foundation of China and grant CSTC 2008BB5126 from the Natural Science Foundation of ChongQing. The authors would also like to thank Dr. Yan Hwa Wu Lee (National Yang-Ming University in Taiwan) for provision of recombinant plasmid containing HCVc gene, PGST-HCVc195.

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Authors and Affiliations

  1. Institute of Hepatobiliary Surgery of PLA, Southwest Hospital, Third Military Medical University, ChongQing, China

    Tianyu Li PhD, Dajiang Li PhD, Long Cheng PhD, Hongye Wu MM, Zhanfeng Gao PhD, Zipei Liu PhD, Weiwei Jiang PhD, Ying Hong Gao MM, Feng Tian MM, Lijin Zhao PhD & Shuguang Wang PhD

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  1. Tianyu Li PhD
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  2. Dajiang Li PhD
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  3. Long Cheng PhD
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Corresponding author

Correspondence to Shuguang Wang PhD.

Additional information

Tianyu Li and Dajiang Li contributed equally to this paper.

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Li, T., Li, D., Cheng, L. et al. Epithelial-Mesenchymal Transition Induced by Hepatitis C Virus Core Protein in Cholangiocarcinoma. Ann Surg Oncol 17, 1937–1944 (2010). https://doi.org/10.1245/s10434-010-0925-3

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  • DOI: https://doi.org/10.1245/s10434-010-0925-3

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