H2A.Z regulates tumorigenesis, metastasis and sensitivity to cisplatin in intrahepatic cholangiocarcinoma

Yang,Beng; Tong,Rongliang; Liu,Hua; Wu,Jingbang; Chen,Diyu; Xue,Zhengze; Ding,Chaofeng; Zhou,Lin; Xie,Haiyang; Wu,Jian; Zheng,Shusen

doi:10.3892/ijo.2018.4292

H2A.Z regulates tumorigenesis, metastasis and sensitivity to cisplatin in intrahepatic cholangiocarcinoma

Authors:
- Beng Yang
- Rongliang Tong
- Hua Liu
- Jingbang Wu
- Diyu Chen
- Zhengze Xue
- Chaofeng Ding
- Lin Zhou
- Haiyang Xie
- Jian Wu
- Shusen Zheng
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Affiliations: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang 310003, P.R. China, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang 310003, P.R. China
Published online on: February 28, 2018 https://doi.org/10.3892/ijo.2018.4292
Pages: 1235-1245
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intrahepatic cholangiocarcinoma (ICC) is a fatal, malignant tumor of the liver; effective diagnostic biomarkers and therapeutic targets for ICC have not been identified yet. High expression of H2A histone family member Z (H2A.Z) is a high-risk factor for poor prognosis in patients with breast cancer and primary hepatocellular cancer. However, the significance of H2A.Z and its expression in ICC remains unknown. The present study demonstrated that H2A.Z is overexpressed in ICC and expression of H2A.Z correlated with poor prognosis in patients with ICC. H2A.Z regulated cell proliferation in vitro and in vivo via H2A.Z/S-phase kinase-associated protein 2/p27/p21 signaling. Inhibition of H2A.Z reduced cell proliferation and induced apoptosis in ICC. In addition, downregulation of H2AZ reduced tumor metastasis by repressing epithelial-mesenchymal transition and enhanced the antitumor effects of cisplatin in the treatment of ICC. Overall, H2A.Z promoted cell proliferation and epithelial-mesenchymal transition in ICC, suggesting that H2A.Z may be a novel biomarker and therapeutic target for ICC.

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