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Article

c-Jun N-terminal kinase inhibitor favors transforming growth factor‑β to antagonize hepatitis B virus X protein‑induced cell growth promotion in hepatocellular carcinoma

  • Authors:
    • Yan‑Hui Wu
    • Xi Ai
    • Fu‑Yao Liu
    • Hui‑Fang Liang
    • Bi‑Xiang Zhang
    • Xiao‑Ping Chen
  • View Affiliations / Copyright

    Affiliations: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
  • Pages: 1345-1352
    |
    Published online on: December 4, 2015
       https://doi.org/10.3892/mmr.2015.4644
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Abstract

Transforming growth factor (TGF)‑β induces cell growth arrest in well‑differentiated hepatocellular carcinoma (HCC) while hepatitis B virus X protein (HBx) minimizes the tumor suppression of TGF‑β signaling in early chronic hepatitis B. However, how to reverse the oncogenic effect of HBx and sustain the tumor‑suppressive action of TGF‑β has yet to be investigated. The present study examined the effect of TGF‑β and a c-Jun N-terminal kinase (JNK) inhibitor on cell growth in HCC cells with forced expression of HBx. It was found that HBx promoted cell growth via activation of the JNK/pSMAD3L pathway and inhibition of the transforming growth factor-beta type I receptor (TβRI)/pSMAD3C pathway. pSMAD3L/SMAD4 and pSMAD3C/SMAD4 complexes antagonized each other to regulate c‑Myc expression. In the absence of HBx, TGF‑β induced cell growth arrest through activation of the TβRI/pSMAD3C pathway in well‑differentiated HCC cells. In the presence of HBx, TGF‑β had no effect on cell growth. JNK inhibitor SP600125 significantly reversed the oncogenic action of HBx and favored TGF‑β to regain the ability to inhibit the cell growth in HBx‑expressing well‑differentiated HCC cells. In conclusion, targeting JNK signaling favors TGF‑β to block HBx‑induced cell growth promotion in well‑differentiated HCC cells. As an adjunct to anti‑viral therapy, the combination of TGF‑β and inhibition of JNK signaling is a potential therapy for HBV‑infected HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Wu YH, Ai X, Liu FY, Liang HF, Zhang BX and Chen XP: c-Jun N-terminal kinase inhibitor favors transforming growth factor‑β to antagonize hepatitis B virus X protein‑induced cell growth promotion in hepatocellular carcinoma. Mol Med Rep 13: 1345-1352, 2016.
APA
Wu, Y., Ai, X., Liu, F., Liang, H., Zhang, B., & Chen, X. (2016). c-Jun N-terminal kinase inhibitor favors transforming growth factor‑β to antagonize hepatitis B virus X protein‑induced cell growth promotion in hepatocellular carcinoma. Molecular Medicine Reports, 13, 1345-1352. https://doi.org/10.3892/mmr.2015.4644
MLA
Wu, Y., Ai, X., Liu, F., Liang, H., Zhang, B., Chen, X."c-Jun N-terminal kinase inhibitor favors transforming growth factor‑β to antagonize hepatitis B virus X protein‑induced cell growth promotion in hepatocellular carcinoma". Molecular Medicine Reports 13.2 (2016): 1345-1352.
Chicago
Wu, Y., Ai, X., Liu, F., Liang, H., Zhang, B., Chen, X."c-Jun N-terminal kinase inhibitor favors transforming growth factor‑β to antagonize hepatitis B virus X protein‑induced cell growth promotion in hepatocellular carcinoma". Molecular Medicine Reports 13, no. 2 (2016): 1345-1352. https://doi.org/10.3892/mmr.2015.4644
Copy and paste a formatted citation
x
Spandidos Publications style
Wu YH, Ai X, Liu FY, Liang HF, Zhang BX and Chen XP: c-Jun N-terminal kinase inhibitor favors transforming growth factor‑β to antagonize hepatitis B virus X protein‑induced cell growth promotion in hepatocellular carcinoma. Mol Med Rep 13: 1345-1352, 2016.
APA
Wu, Y., Ai, X., Liu, F., Liang, H., Zhang, B., & Chen, X. (2016). c-Jun N-terminal kinase inhibitor favors transforming growth factor‑β to antagonize hepatitis B virus X protein‑induced cell growth promotion in hepatocellular carcinoma. Molecular Medicine Reports, 13, 1345-1352. https://doi.org/10.3892/mmr.2015.4644
MLA
Wu, Y., Ai, X., Liu, F., Liang, H., Zhang, B., Chen, X."c-Jun N-terminal kinase inhibitor favors transforming growth factor‑β to antagonize hepatitis B virus X protein‑induced cell growth promotion in hepatocellular carcinoma". Molecular Medicine Reports 13.2 (2016): 1345-1352.
Chicago
Wu, Y., Ai, X., Liu, F., Liang, H., Zhang, B., Chen, X."c-Jun N-terminal kinase inhibitor favors transforming growth factor‑β to antagonize hepatitis B virus X protein‑induced cell growth promotion in hepatocellular carcinoma". Molecular Medicine Reports 13, no. 2 (2016): 1345-1352. https://doi.org/10.3892/mmr.2015.4644
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