Skip to main content
SpringerLink
Log in

Overexpression of Hiwi Inhibits the Growth and Migration of Chronic Myeloid Leukemia Cells

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Chronic myeloid leukemia (CML) is a hematopoietic malignancy characterized by dysregulated growth and proliferation of hematopoietic stem/progenitor cells in bone marrow and excessive expansion of hematopoietic compartments in peripheral blood. Expression deletion of Hiwi, a human Piwi homolog, has been reported to be implicated in leukemogenesis. We here explored Hiwi’s role in CML pathogenesis by determining how and whether its forced overexpression could affect CML cell growth and migration. The present results showed that lentivirus-mediated overexpression of Hiwi significantly suppressed cell proliferation and induced obvious apoptosis in K562 cells, a CML line cell line. Tumors in BALB/c nude mice generated by the K562 cells expressing Hiwi were much smaller than those formed by the control cells. Like in vitro, Hiwi upregulation induced cell apoptosis in the tumor tissues in vivo. Additionally, Hiwi elevation suppressed K562 cell migration and inhibited the activity and expression of matrix metalloproteinase-2 and -9. In summary, our study demonstrates that Hiwi overexpression inhibits CML cell growth and migration, providing insights into its role in CML pathogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Deininger, M. W., Goldman, J. M., & Melo, J. V. (2000). The molecular biology of chronic myeloid leukemia. Blood, 96, 3343–3356.

    CAS  PubMed  Google Scholar 

  2. Ma, L., Shan, Y., Bai, R., Xue, L., Eide, C. A., Ou, J., et al. (2014). A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia. Science Translational Medicine, 6, 252ra121. doi:10.1126/scitranslmed.3009073.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Baccarani, M., Deininger, M. W., Rosti, G., Hochhaus, A., Soverini, S., Apperley, J. F., et al. (2013). European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood, 122, 872–884.

    Article  CAS  PubMed  Google Scholar 

  4. Soverini, S., Hochhaus, A., Nicolini, F. E., Gruber, F., Lange, T., Saglio, G., et al. (2011). BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood, 118, 1208–1215.

    Article  CAS  PubMed  Google Scholar 

  5. Cox, D. N., Chao, A., Baker, J., Chang, L., Qiao, D., & Lin, H. (1998). A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes & Development, 12, 3715–3727.

    Article  CAS  Google Scholar 

  6. Siomi, M. C., Sato, K., Pezic, D., & Aravin, A. A. (2011). PIWI-interacting small RNAs: the vanguard of genome defence. Nature Reviews Molecular Cell Biology, 12, 246–258.

    Article  CAS  PubMed  Google Scholar 

  7. Qiao, D., Zeeman, A. M., Deng, W., Looijenga, L. H., & Lin, H. (2002). Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene, 21, 3988–3999.

    Article  CAS  PubMed  Google Scholar 

  8. Liu, W., Gao, Q., Chen, K., Xue, X., Li, M., Chen, Q., et al. (2014). Hiwi facilitates chemoresistance as a cancer stem cell marker in cervical cancer. Oncology Reports, 32, 1853–1860.

    CAS  PubMed  Google Scholar 

  9. Liang, D., Fang, Z., Dong, M., Liang, C., Xing, C., Zhao, J., & Yang, Y. (2012). Effect of RNA interference-related HiWi gene expression on the proliferation and apoptosis of lung cancer stem cells. Oncology Letters, 4, 146–150.

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Sharma, A. K., Nelson, M. C., Brandt, J. E., Wessman, M., Mahmud, N., Weller, K. P., & Hoffman, R. (2001). Human CD34(+) stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi. Blood, 97, 426–434.

    Article  CAS  PubMed  Google Scholar 

  11. Favaro, P., Traina, F., Machado-Neto, J. A., Lazarini, M., Lopes, M. R., Pereira, J. K., et al. (2013). FMNL1 promotes proliferation and migration of leukemia cells. Journal of Leukocyte Biology, 94, 503–512.

    Article  CAS  PubMed  Google Scholar 

  12. Liu, W. H., Chen, Y. J., Chien, J. H., & Chang, L. S. (2014). Amsacrine suppresses matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia cells. Journal of Cellular Physiology, 229, 588–598.

    Article  CAS  PubMed  Google Scholar 

  13. Grochola, L. F., Greither, T., Taubert, H., Moller, P., Knippschild, U., Udelnow, A., et al. (2008). The stem cell-associated Hiwi gene in human adenocarcinoma of the pancreas: expression and risk of tumour-related death. British Journal of Cancer, 99, 1083–1088.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Pardal, R., Clarke, M. F., & Morrison, S. J. (2003). Applying the principles of stem-cell biology to cancer. Nature Reviews Cancer, 3, 895–902.

    Article  CAS  PubMed  Google Scholar 

  15. Al-Hajj, M., & Clarke, M. F. (2004). Self-renewal and solid tumor stem cells. Oncogene, 23, 7274–7282.

    Article  CAS  PubMed  Google Scholar 

  16. Liu, X., Sun, Y., Guo, J., Ma, H., Li, J., Dong, B., et al. (2006). Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. International Journal of Cancer, 118, 1922–1929.

    Article  CAS  Google Scholar 

  17. Wang, D. W., Wang, Z. H., Wang, L. L., Song, Y., & Zhang, G. Z. (2014). Overexpression of hiwi promotes growth of human breast cancer cells. Asian Pacific Journal of Cancer Prevention, 15, 7553–7558.

    Article  PubMed  Google Scholar 

  18. Wang, X., Tong, X., Gao, H., Yan, X., Xu, X., Sun, S., et al. (2014). Silencing HIWI suppresses the growth, invasion and migration of glioma cells. International Journal of Oncology, 45, 2385–2392.

    CAS  PubMed  Google Scholar 

  19. Xie, Y., Yang, Y., Ji, D., Zhang, D., Yao, X., & Zhang, X. (2015). Hiwi downregulation, mediated by shRNA, reduces the proliferation and migration of human hepatocellular carcinoma cells. Molecular Medicine Reports, 11, 1455–1461.

    CAS  PubMed  Google Scholar 

  20. De Oliveira, F., Chauvin, C., Ronot, X., Mousseau, M., Leverve, X., & Fontaine, E. (2006). Effects of permeability transition inhibition and decrease in cytochrome c content on doxorubicin toxicity in K562 cells. Oncogene, 25, 2646–2655.

    Article  PubMed  Google Scholar 

  21. Zhang, J. H., Liu, L. Q., He, Y. L., Kong, W. J., & Huang, S. A. (2010). Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells. Acta Pharmacologica Sinica, 31, 861–866.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Kitada, S., Pedersen, I. M., Schimmer, A. D., & Re, J. C. (2002). Dysregulation of apoptosis genes in hematopoietic malignancies. Oncogene, 21, 3459–3474.

    Article  CAS  PubMed  Google Scholar 

  23. Wong, R. S. (2011). Apoptosis in cancer: from pathogenesis to treatment. Journal of Experimental & Clinical Cancer Research, 30, 87.

    Article  CAS  Google Scholar 

  24. Sawyers, C. L., Hochhaus, A., Feldman, E., Goldman, J. M., Miller, C. B., Ottmann, O. G., et al. (2002). Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood, 99, 3530–3539.

    Article  CAS  PubMed  Google Scholar 

  25. Lim, S. L., Ricciardelli, C., Oehler, M. K., Tan, I. M., Russell, D., & Grutzner, F. (2014). Overexpression of piRNA pathway genes in epithelial ovarian cancer. PLoS One, 9, e99687.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Overall, C. M., & Lopez-Otin, C. (2002). Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nature Reviews Cancer, 2, 657–672.

    Article  CAS  PubMed  Google Scholar 

  27. Ugarte-Berzal, E., Redondo-Munoz, J., Eroles, P., Del Cerro, M. H., Garcia-Marco, J. A., Terol, M. J., & Garcia-Pardo, A. (2010). VEGF/VEGFR2 interaction down-regulates matrix metalloproteinase-9 via STAT1 activation and inhibits B chronic lymphocytic leukemia cell migration. Blood, 115, 846–849.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a Grant from the Foundation of Department of Science and Technology, Jilin Province (No. 200705181).

Author information

Author notes

    Authors and Affiliations

    1. Cancer Center, The First Hospital of Jilin University, 71 Xinmin Avenue, Changchun, Jilin, 130021, People’s Republic of China

      Yalin Wang, Yan Jiang, Bailu Sang, Xiaolin Hu, Xiaofeng Cong & Ziling Liu

    2. Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China

      Ning Ma

    Authors
    1. Yalin Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Yan Jiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Ning Ma
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Bailu Sang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Xiaolin Hu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Xiaofeng Cong
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Ziling Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Ziling Liu.

    Additional information

    Yalin Wang and Yan Jiang have contributed equally to this study.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Wang, Y., Jiang, Y., Ma, N. et al. Overexpression of Hiwi Inhibits the Growth and Migration of Chronic Myeloid Leukemia Cells. Cell Biochem Biophys 73, 117–124 (2015). https://doi.org/10.1007/s12013-015-0651-3

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12013-015-0651-3

    Keywords

    Search

    Navigation