ISG15 inhibits cancer cell growth and promotes apoptosis

  • Authors:
    • Mei-Juan Zhou
    • Fang-Zhi Chen
    • Han-Chun Chen
    • Xin-Xing Wan
    • Xi Zhou
    • Qian Fang
    • Dian-Zheng Zhang
  • View Affiliations

  • Published online on: December 30, 2016     https://doi.org/10.3892/ijmm.2016.2845
  • Pages: 446-452
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Abstract

Cervical cancer is one of the most common causes of cancer-related mortality in women in developing countries. Interferon (IFN)-α has been widely used in the treatment of various types of cancer, including cervical cancer, and IFN-stimulated gene 15 (ISG15), an ubiquitin-like protein, is upregulated by IFN-α treatment. The anti-virus and antitumor effects of ISG15 have been reported; however, its mechanism of action have not yet been fully elucidated. In this study, HeLa cells were used as a model system to investigate the roles of ISG15 in IFN-α-mediated cancer cell growth inhibition and induction of apoptosis. The results revealed that both p53 and p21 were upregulated in HeLa cells treated with IFN-α or in the HeLa cells overexpressing ISG15. In addition, the expression levels of ubiquitin-like modifier-activating enzyme 7 (UBA7, also known as UBE1L; ISG15 E1-activating enzyme), UBCH8 (ISG15 E2-conjugating enzyme) and HERC5 (ISG15 E3-ligase) were elevated in the HeLa cells treated with IFN-α. The levels of p53 in the HeLa cells were attenuated by transient transfection with small interfering RNA (siRNA) targeting ISG15 (ISG15-siRNA). Cell viability was inhibited by both IFN-α treatment and ISG15 overexpression. However, these effects were significantly diminished when p53 was knocked down, suggesting that the effects of inhibitory effects of ISG15 on HeLa cell growth and the induction of apoptosis were p53-dependent. Taken together, these results suggest the existence of the IFN-α/ISG15/p53 axis in cervical cancer cells and any strategies manipulating the levels of ISG15 may thus prove to be effective in the treatment of cervical cancer.
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February-2017
Volume 39 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhou M, Chen F, Chen H, Wan X, Zhou X, Fang Q and Zhang D: ISG15 inhibits cancer cell growth and promotes apoptosis. Int J Mol Med 39: 446-452, 2017.
APA
Zhou, M., Chen, F., Chen, H., Wan, X., Zhou, X., Fang, Q., & Zhang, D. (2017). ISG15 inhibits cancer cell growth and promotes apoptosis. International Journal of Molecular Medicine, 39, 446-452. https://doi.org/10.3892/ijmm.2016.2845
MLA
Zhou, M., Chen, F., Chen, H., Wan, X., Zhou, X., Fang, Q., Zhang, D."ISG15 inhibits cancer cell growth and promotes apoptosis". International Journal of Molecular Medicine 39.2 (2017): 446-452.
Chicago
Zhou, M., Chen, F., Chen, H., Wan, X., Zhou, X., Fang, Q., Zhang, D."ISG15 inhibits cancer cell growth and promotes apoptosis". International Journal of Molecular Medicine 39, no. 2 (2017): 446-452. https://doi.org/10.3892/ijmm.2016.2845