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Article

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
  • View Affiliations / Copyright

    Affiliations: Bone Marrow Transplantation Center, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, P.R. China, Zhejiang Cancer Hospital, Hangzhou 310022, P.R. China
  • Pages: 351-359
    |
    Published online on: October 30, 2014
       https://doi.org/10.3892/ijo.2014.2738
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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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1 

Borden EC, Sen GC, Uze G, et al: Interferons at age 50: past, current and future impact on biomedicine. Nat Rev Drug Discov. 6:975–990. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Preudhomme C, Guilhot J, Nicolini FE, et al: Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 363:2511–2521. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Simonsson B, Gedde-Dahl T, Markevarn B, et al: Combination of pegylated IFN-alpha2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood. 118:3228–3235. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Talpaz M, Hehlmann R, Quintas-Cardama A, Mercer J and Cortes J: Re-emergence of interferon-alpha in the treatment of chronic myeloid leukemia. Leukemia. 27:803–812. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Jin LH, Tabe Y, Konoplev S, et al: CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells. Mol Cancer Ther. 7:48–58. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Zhang B, Li M, McDonald T, et al: Microenvironmental protection of CML stem and progenitor cells from tyrosine kinase inhibitors through N-cadherin and Wnt-beta-catenin signaling. Blood. 121:1824–1838. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Plimack ER, Desai JR, Issa JP, et al: A phase I study of decitabine with pegylated interferon alpha-2b in advanced melanoma: impact on DNA methylation and lymphocyte populations. Invest New Drugs. 32:969–975. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Abukawa H, Kaban LB, Williams WB, Terada S, Vacanti JP and Troulis MJ: Effect of interferon-alpha-2b on porcine mesenchymal stem cells. J Oral Maxillofac Surg. 64:1214–1220. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Oreffo RO, Romberg S, Virdi AS, Joyner CJ, Berven S and Triffitt JT: Effects of interferon alpha on human osteoprogenitor cell growth and differentiation in vitro. J Cell Biochem. 74:372–385. 1999. View Article : Google Scholar : PubMed/NCBI

10 

Lee BS, Stewart EA, Sahakian M and Nowak RA: Interferon-alpha is a potent inhibitor of basic fibroblast growth factor-stimulated cell proliferation in human uterine cells. Am J Reprod Immunol. 40:19–25. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Leaman DW, Chawla-Sarkar M, Jacobs B, et al: Novel growth and death related interferon-stimulated genes (ISGs) in melanoma: greater potency of IFN-beta compared with IFN-alpha2. J Interferon Cytokine Res. 23:745–756. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Hatzfeld A, Eid P, Peiffer I, et al: A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β. Leukemia. 21:714–724. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Crowder C, Dahle O, Davis RE, Gabrielsen OS and Rudikoff S: PML mediates IFN-alpha-induced apoptosis in myeloma by regulating TRAIL induction. Blood. 105:1280–1287. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Everett RD and Chelbi-Alix MK: PML and PML nuclear bodies: implications in antiviral defence. Biochimie. 89:819–830. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Zhou W and Bao S: PML-mediated signaling and its role in cancer stem cells. Oncogene. 33:1475–1484. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Salomoni P: Stemming out of a new PML era? Cell Death Differ. 16:1083–1092. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Salomoni P, Dvorkina M and Michod D: Role of the promyelocytic leukaemia protein in cell death regulation. Cell Death Dis. 3:e2472012. View Article : Google Scholar : PubMed/NCBI

18 

Sun J, Fu S, Zhong W and Huang H: PML overexpression inhibits proliferation and promotes the osteogenic differentiation of human mesenchymal stem cells. Oncol Rep. 30:2785–2794. 2013.PubMed/NCBI

19 

Conget PA and Minguell JJ: Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol. 181:67–73. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Sperka T, Wang J and Rudolph KL: DNA damage checkpoints in stem cells, ageing and cancer. Nat Rev Mol Cell Biol. 13:579–590. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Ben-Porath I and Weinberg RA: When cells get stressed: an integrative view of cellular senescence. J Clin Invest. 113:8–13. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Campisi J: Aging, cellular senescence, and cancer. Annu Rev Physiol. 75:685–705. 2013. View Article : Google Scholar

23 

Sikora E, Arendt T, Bennett M and Narita M: Impact of cellular senescence signature on ageing research. Ageing Res Rev. 10:146–152. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Upreti M, Koonce NA, Hennings L, Chambers TC and Griffin RJ: Pegylated IFN-alpha sensitizes melanoma cells to chemotherapy and causes premature senescence in endothelial cells by IRF-1 mediated signaling. Cell Death Dis. 1:e672010. View Article : Google Scholar : PubMed/NCBI

25 

Li Q, Tang L, Roberts PC, et al: Interferon regulatory factors IRF5 and IRF7 inhibit growth and induce senescence in immortal Li-Fraumeni fibroblasts. Mol Cancer Res. 6:770–784. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Burchert A, Wolfl S, Schmidt M, et al: Interferon-alpha, but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia. Blood. 101:259–264. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Bischof O, Kirsh O, Pearson M, Itahana K, Pelicci PG and Dejean A: Deconstructing PML-induced premature senescence. EMBO J. 21:3358–3369. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Vernier M, Bourdeau V, Gaumont-Leclerc MF, et al: Regulation of E2Fs and senescence by PML nuclear bodies. Genes Dev. 25:41–50. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Kruse JP and Gu W: Modes of p53 regulation. Cell. 137:609–622. 2009. View Article : Google Scholar

30 

Sung KS, Lee YA, Kim ET, Lee SR, Ahn JH and Choi CY: Role of the SUMO-interacting motif in HIPK2 targeting to the PML nuclear bodies and regulation of p53. Exp Cell Res. 317:1060–1070. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Xue Y, Li L, Zhang D, et al: Telomerase suppression initiates PML-dependent p53 activation to inhibit bladder cancer cell growth. Oncol Rep. 24:1551–1559. 2010.PubMed/NCBI

32 

Midgley CA and Lane DP: p53 protein stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding. Oncogene. 15:1179–1189. 1997. View Article : Google Scholar : PubMed/NCBI

33 

Michael D and Oren M: The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 13:49–58. 2003. View Article : Google Scholar : PubMed/NCBI

34 

Dai C and Gu W: p53 post-translational modification: deregulated in tumorigenesis. Trends Mol Med. 16:528–536. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Carracedo A, Ito K and Pandolfi PP: The nuclear bodies inside out: PML conquers the cytoplasm. Curr Opin Cell Biol. 23:360–366. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Fu S, Wei J, Wang G, Wang B, Wang Y, Lai X and Huang H: The key role of PML in IFN-α induced cellular senescence of human mesenchymal stromal cells. Int J Oncol 46: 351-359, 2015.
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
Copy and paste a formatted citation
x
Spandidos Publications style
Fu S, Wei J, Wang G, Wang B, Wang Y, Lai X and Huang H: The key role of PML in IFN-α induced cellular senescence of human mesenchymal stromal cells. Int J Oncol 46: 351-359, 2015.
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
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