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Inhibition of SOX4 induces melanoma cell apoptosis via downregulation of NF-κB p65 signaling

  • Authors:
    • Qiong Cheng
    • Juan Du
    • Lin Xie
    • Xiao Liu
    • Zheng Li
    • Fuguo Zuo
    • Jinfeng Wu
    • Jinhua Xu

  • View Affiliations

  • Published online on: May 16, 2018     https://doi.org/10.3892/or.2018.6443
  • Pages: 369-376
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Abstract

SOX4 (SRY Box 4) has attracted attention due to its important effects on cell growth, proliferation and apoptosis, among other cellular processes. However, the role of SOX4 in melanoma cell apoptosis remains unclear. In the present study, we investigated whether inhibition of SOX4 induces melanoma cell apoptosis, and explored the possible mechanism involving the NF-κB signaling pathway. SOX4 was knocked down using a lentivirus in melanoma A2058 and SK-MEL-5 cell lines. Cell proliferation was measured by MTT assay. Apoptosis was determined by flow cytometry. Western blotting was performed to detect the protein levels of SOX4, p65 and apoptosis-related proteins, such as PARP, Bcl-2, Bax and survivin. Quantitative real-time PCR (qRT-PCR) was used to examine the mRNA levels of SOX4 and p65. To determine whether SOX4 is able to bind to the promoter of p65, a CHIP-PCR assay was performed. Our data demonstrated that SOX4 knockdown significantly induced apoptosis in melanoma cells, which was accompanied by increases in cleaved PARP and Bax, and decreases in Bcl-2 and survivin. The expression of p65 was also decreased in SOX4-knockdown melanoma cells. The CHIP-PCR assay indicated that SOX4 was able to bind to the promoter region of p65. We also observed that apoptosis in SOX4-knockdown and p65-overexpressing A2058 cells was much lower than that in SOX4-knockdown alone cells. This revealed that the overexpression of p65 partially reversed SOX4 downregulation-induced apoptosis. In conclusion, our results demonstrated that inhibition of SOX4 markedly induced melanoma cell apoptosis via downregulation of the NF-κB signaling pathway, which thus may be a novel approach for the treatment of melanoma.
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July-2018
Volume 40 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Cheng Q, Du J, Xie L, Liu X, Li Z, Zuo F, Wu J and Xu J: Inhibition of SOX4 induces melanoma cell apoptosis via downregulation of NF-κB p65 signaling. Oncol Rep 40: 369-376, 2018.
APA
Cheng, Q., Du, J., Xie, L., Liu, X., Li, Z., Zuo, F. ... Xu, J. (2018). Inhibition of SOX4 induces melanoma cell apoptosis via downregulation of NF-κB p65 signaling. Oncology Reports, 40, 369-376. https://doi.org/10.3892/or.2018.6443
MLA
Cheng, Q., Du, J., Xie, L., Liu, X., Li, Z., Zuo, F., Wu, J., Xu, J."Inhibition of SOX4 induces melanoma cell apoptosis via downregulation of NF-κB p65 signaling". Oncology Reports 40.1 (2018): 369-376.
Chicago
Cheng, Q., Du, J., Xie, L., Liu, X., Li, Z., Zuo, F., Wu, J., Xu, J."Inhibition of SOX4 induces melanoma cell apoptosis via downregulation of NF-κB p65 signaling". Oncology Reports 40, no. 1 (2018): 369-376. https://doi.org/10.3892/or.2018.6443