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RIP1 upregulation promoted tumor progression by activating AKT/Bcl-2/BAX signaling and predicted poor postsurgical prognosis in HCC

Tumor Biology volume 37, pages 15305–15313 (2016)Cite this article

Abstract

Although growing body of evidences have identified a critical role for receptor-interacting protein kinase 1 (RIP1) in mediating cell death signaling, its possible contribution to hepatocellular carcinoma (HCC) progression remains unclear. Here, we displayed that expression of RIP1 was significantly upregulated in HCC tissues than in adjacent liver tissues from 81.9 % HCC patients (P < 0.001) by immunohistochemistry (IHC) staining. Overexpression of RIP1 was found positively associated with HBV infection, advanced TNM staging, portal vein invasion, and intrahepatic metastases. Kaplan-Meier curve analysis indicated that patients with higher RIP1 expression in HCC tissues suffered from unfavorable postsurgical survival. Higher RIP1 expression in HCC tissues was also confirmed to be an independent poor prognostic predictor. Knockdown of RIP1 resulted in suppression of cell viability and proliferation and induced cell apoptosis in MHCC97h cells. Nevertheless, enforced expression of RIP1 promoted cell viability and proliferation of Huh7 cells and inhibited cell apoptosis. Mechanistic studies revealed that RIP1 exerted its function on HCC progression via activating AKT/Bcl-2/BAX signaling. In conclusion, our results provided the evidence of RIP1 overexpression in HCC, and RIP1 could be a novel predictive factor of unfavorable prognosis in HCC patients. Activation of AKT/Bcl-2/BAX signaling contributed to RIP1 promoting HCC progression.

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Acknowledgments

This study was supported by grants from the National Natural Scientific Foundation of China (81301743 and 81572733 to Xin Zheng), Research Fund for the doctoral Program of High Education of China from Ministry of Education (no. 20120201120090 to Xin Zheng), Key Science and Technology Program of Shaanxi Province (no. 2014K11-01-01-21 to Xin Zheng), and the Fundamental Research Funds for the Basic Research Operating expenses Program of Central College sponsored by Xi’an Jiaotong University to Xin Zheng.

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Affiliations

  1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an, Shaanxi, 710061, China

    Cong Wang, Bowen Yao, Meng Xu & Xin Zheng

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  1. Cong Wang
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  2. Bowen Yao
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  3. Meng Xu
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  4. Xin Zheng
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Correspondence to Xin Zheng.

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Ethical statement

The study was reviewed and approved by the ethics committee of the First Affiliated Hospital of Xi’an Jiaotong University according to the Helsinki Declaration of 1975 (no. 20080301, 6 May 2008).

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None.

Additional information

Cong Wang and Bowen Yao contributed equally to this work.

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Cite this article

Wang, C., Yao, B., Xu, M. et al. RIP1 upregulation promoted tumor progression by activating AKT/Bcl-2/BAX signaling and predicted poor postsurgical prognosis in HCC. Tumor Biol. 37, 15305–15313 (2016). https://doi.org/10.1007/s13277-016-5342-1

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  • DOI: https://doi.org/10.1007/s13277-016-5342-1

Keywords

  • RIP1
  • HCC
  • AKT
  • Bcl-2/BAX
  • Prognosis