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Article

Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells

  • Authors:
    • Yi-Deun Jung
    • Jae-Woong Shim
    • Seong-Joon Park
    • Si Ho Choi
    • Kwangmo Yang
    • Kyu Heo
    • Moon-Taek Park
  • View Affiliations / Copyright

    Affiliations: Research Center, Dongnam Institute of Radiological and Medical Sciences (DIRAMS), Busan 619-953, Republic of Korea
  • Pages: 1232-1242
    |
    Published online on: December 30, 2014
       https://doi.org/10.3892/ijo.2014.2813
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Abstract

Activation of epithelial-mesenchymal transition (EMT) is important for malignant tumor progression exhibiting migratory and invasive properties. UHRF1 (ubiquitin-like, with PHD and RING finger domains 1), as an epigenetic regulator, plays a crucial role in DNA CpG methylation, chromatin remodeling and gene expression. Many studies demonstrated that UHRF1 is aberrantly expressed in various types of human cancer. However, the precise role of UHRF1 in human cancers remains highly controversial. In the present study, we found that downregulation of UHRF1 enhances the migratory and invasive properties of human cancer cells by inducing EMT, and that the CXCR4 signaling pathway is strictly necessary for UHRF1 deficiency-mediated induction of EMT. Downregulation of UHRF1 induced the expression of the EMT-regulating transcription factors, Zeb1, Slug and Snail and then led to decreased protein level of E-cadherin, and increased protein level of N-cadherin and vimentin, including increased migratory and invasive properties of human cancer cells. In addition, siRNA targeting of Zeb1 or Snail effectively attenuated UHRF1 deficiency-induced EMT, but siRNA targeting of Slug did not, indicating that Zeb1 and Snail play key roles in this event. Moreover, downregulation of UHRF1 induced the expression of CXCR4 in HepG2 cells. siRNA targeting of CXCR4 greatly suppressed the UHRF1 deficiency-induced EMT, as evidenced by a reversal of expression patterns of Snail and Zeb1, and by reduced migratory and invasive properties of HepG2 cells. In conclusion, our results demonstrate that downregulation of UHRF1 contributes to the induction of EMT in human cancer cells via the activation of CXCR4 signaling pathway. Our observation also suggests that UHRF1 may play a pivotal role in suppressing the malignant alteration of cancer cells.
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Copy and paste a formatted citation
Spandidos Publications style
Jung Y, Shim J, Park S, Choi SH, Yang K, Heo K and Park M: Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells. Int J Oncol 46: 1232-1242, 2015.
APA
Jung, Y., Shim, J., Park, S., Choi, S.H., Yang, K., Heo, K., & Park, M. (2015). Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells. International Journal of Oncology, 46, 1232-1242. https://doi.org/10.3892/ijo.2014.2813
MLA
Jung, Y., Shim, J., Park, S., Choi, S. H., Yang, K., Heo, K., Park, M."Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells". International Journal of Oncology 46.3 (2015): 1232-1242.
Chicago
Jung, Y., Shim, J., Park, S., Choi, S. H., Yang, K., Heo, K., Park, M."Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells". International Journal of Oncology 46, no. 3 (2015): 1232-1242. https://doi.org/10.3892/ijo.2014.2813
Copy and paste a formatted citation
x
Spandidos Publications style
Jung Y, Shim J, Park S, Choi SH, Yang K, Heo K and Park M: Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells. Int J Oncol 46: 1232-1242, 2015.
APA
Jung, Y., Shim, J., Park, S., Choi, S.H., Yang, K., Heo, K., & Park, M. (2015). Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells. International Journal of Oncology, 46, 1232-1242. https://doi.org/10.3892/ijo.2014.2813
MLA
Jung, Y., Shim, J., Park, S., Choi, S. H., Yang, K., Heo, K., Park, M."Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells". International Journal of Oncology 46.3 (2015): 1232-1242.
Chicago
Jung, Y., Shim, J., Park, S., Choi, S. H., Yang, K., Heo, K., Park, M."Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells". International Journal of Oncology 46, no. 3 (2015): 1232-1242. https://doi.org/10.3892/ijo.2014.2813
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