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Article

The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression

  • Authors:
    • Zhen Yang
    • Sun Yang
    • Bobbye J. Misner
    • Feng Liu-Smith
    • Frank L. Meyskens
  • View Affiliations / Copyright

    Affiliations: Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Chao Family Comprehensive Cancer Center, University of California-Irvine, Irvine, CA, USA
  • Pages: 1820-1828
    |
    Published online on: August 8, 2014
       https://doi.org/10.3892/ijo.2014.2589
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Abstract

Hepatocellular carcinoma (HCC) is responsible for a third of the estimated cancer-caused deaths worldwide. To deeply understand the mechanisms controlling HCC progression is of primary importance to develop new approaches for treatment. Apurinic/apyrimidinic endonuclease-1/redox effector factor 1 (APE/Ref-1) has been uncovered elevated in various types of cancer, including HCC. Additionally, HCC progression is always correlated with elevated copper (Cu). Our previous data demonstrated that Cu treatment initiated APE/Ref-1 expression and its downstream targets. Therefore, we hypothesized that APE/Ref-1 may be involved in HCC progression through mediating the effect of Cu to its signaling cascades. Following different treatments, human HCC cell line (Hep3B) and immortalized non-malignant hepatocyte cell line (THLE3) were analyzed to explore the role of APE/Ref-1 signaling pathway. Unstained human tissue microarrays (TMA) were subjected to IHC analysis to study the relationship between APE/Ref-1 expression and clinic features. APE/Ref-1 was upregulated in HCC cells consistent with the strong expression of APE/Ref-1 in HCC tissue microarray. Greater cytoplasmic accumulation of APE/Ref-1 was found in poorly differentiated and more aggressive tumors. Also we provide evidence to show that APE/Ref-1 signaling pathway stimulates cellular proliferation, enhances anti-apoptosis, and facilitates metastasis through experimental knockdown of APE/Ref-1 using siRNA in Hep3B cells or overexpressing APE/Ref-1 in THLE3 cells. These results define a novel role of APE/Ref-1 in HCC progression as being an important mediating and potentiating molecule, and also provide a basis for further investigations utilizing appropriate APE/Ref-1 inhibitors in combination with chemo-drugs for HCC treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Yang Z, Yang S, Misner BJ, Liu-Smith F and Meyskens FL: The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression. Int J Oncol 45: 1820-1828, 2014.
APA
Yang, Z., Yang, S., Misner, B.J., Liu-Smith, F., & Meyskens, F.L. (2014). The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression. International Journal of Oncology, 45, 1820-1828. https://doi.org/10.3892/ijo.2014.2589
MLA
Yang, Z., Yang, S., Misner, B. J., Liu-Smith, F., Meyskens, F. L."The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression". International Journal of Oncology 45.5 (2014): 1820-1828.
Chicago
Yang, Z., Yang, S., Misner, B. J., Liu-Smith, F., Meyskens, F. L."The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression". International Journal of Oncology 45, no. 5 (2014): 1820-1828. https://doi.org/10.3892/ijo.2014.2589
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Z, Yang S, Misner BJ, Liu-Smith F and Meyskens FL: The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression. Int J Oncol 45: 1820-1828, 2014.
APA
Yang, Z., Yang, S., Misner, B.J., Liu-Smith, F., & Meyskens, F.L. (2014). The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression. International Journal of Oncology, 45, 1820-1828. https://doi.org/10.3892/ijo.2014.2589
MLA
Yang, Z., Yang, S., Misner, B. J., Liu-Smith, F., Meyskens, F. L."The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression". International Journal of Oncology 45.5 (2014): 1820-1828.
Chicago
Yang, Z., Yang, S., Misner, B. J., Liu-Smith, F., Meyskens, F. L."The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression". International Journal of Oncology 45, no. 5 (2014): 1820-1828. https://doi.org/10.3892/ijo.2014.2589
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