The key role of PML in IFN-α induced cellular senescence of human mesenchymal stromal cells

  • Authors:
    • Shan Fu
    • Jieping Wei
    • Gang Wang
    • Binsheng Wang
    • Yebo Wang
    • Xiaoyu Lai
    • He Huang
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  • Published online on: October 30, 2014     https://doi.org/10.3892/ijo.2014.2738
  • Pages: 351-359
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Abstract

Recent developments and re-emergence of interferon α (IFN-α) have renewed interest in the therapy for patients with chronic myeloid leukemia (CML). Related molecular mechanism may be the direct effect of IFN-α on CML stem cells. Human mesenchymal stromal cells (hMSCs) are important to protect CML stem cells, and IFN-α was described as a potential inhibitor of hMSCs. However, the exact mechanism remains obscure. PML as a known tumor suppressor locates downstream of the IFN-α pathway, and little is known about the PML gene regulation in hMSCs. The aim of this study was to investigate the effects of IFN-α on hMSCs and defined the role of PML involved in this process. Our results suggested that hMSCs incurred senescence upon IFN-α stimulation, while PML levels were observed significant increased. The recombinant lentiviral vector, which encodes shRNA against PML or full-length PML cDNA, was constructed. By knocking-down and overexpressing PML, we found that PML was indispensable to IFN-α mediated hMSC senescence. The molecular mechanism underlying this process may be an increased co-localization of PML and p53 induced by IFN-α. Our data demonstrated that IFN-α can induce cellular senescence of hMSCs and PML plays a key role in this process. These findings provided novel insight into the effect of IFN-α on hMSCs.
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January 2015
Volume 46 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Fu, S., Wei, J., Wang, G., Wang, B., Wang, Y., Lai, X., & Huang, H. (2015). The key role of PML in IFN-α induced cellular senescence of human mesenchymal stromal cells. International Journal of Oncology, 46, 351-359. https://doi.org/10.3892/ijo.2014.2738
MLA
Fu, S., Wei, J., Wang, G., Wang, B., Wang, Y., Lai, X., Huang, H."The key role of PML in IFN-α induced cellular senescence of human mesenchymal stromal cells". International Journal of Oncology 46.1 (2015): 351-359.
Chicago
Fu, S., Wei, J., Wang, G., Wang, B., Wang, Y., Lai, X., Huang, H."The key role of PML in IFN-α induced cellular senescence of human mesenchymal stromal cells". International Journal of Oncology 46, no. 1 (2015): 351-359. https://doi.org/10.3892/ijo.2014.2738