Epigenetic activation of WHSC1 functions as an oncogene and is associated with poor prognosis in cervical cancer

  • Authors:
    • Zhuolian Yin
    • Yong Sun
    • Sufang Ge
    • Juxiang Sun
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  • Published online on: February 17, 2017     https://doi.org/10.3892/or.2017.5463
  • Pages: 2286-2294
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Abstract

Overexpression of Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is commonly observed in various types of tumors. However, the potential mechanism responsible for this molecular event is poorly understood. In the present study, we found that the mRNA levels of WHSC1 were significantly increased in cervical cancer cells, and that CpG sites were almost fully methylated in HaCaT cells, but partially methylated in HeLa and C33A cells. Clinically, the results of quantitative methylation-specific PCR (QMSP) and quantitative real-time PCR (qRT-PCR), showed that methylation levels of the WHSC1 gene were significantly decreased in cervical cancer tumors and inversely correlated with its mRNA expression levels. Both decreased methylation of WHSC1 and increased mRNA were associated with cancer progression and poor prognosis. In addition, overexpression of WHSC1 contributed to cell proliferation, migration and invasion, while cells with WHSC1 knockdown exhibited the opposite effects. AKT/metalloproteinase-2 (MMP-2) signaling was activated and inactivated upon overexpression and silencing of WHSC1, respectively. Silencing of WHSC1 also suppressed tumor growth in a xenograft model. In conclusion, WHSC1 is hypomethylated in cervical cancer, and consequent overexpression of WHSC1 mRNA may promote cervical carcinogenesis by activating the AKT/MMP-2 signaling pathway.
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April-2017
Volume 37 Issue 4

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

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Spandidos Publications style
Yin Z, Sun Y, Ge S and Sun J: Epigenetic activation of WHSC1 functions as an oncogene and is associated with poor prognosis in cervical cancer. Oncol Rep 37: 2286-2294, 2017
APA
Yin, Z., Sun, Y., Ge, S., & Sun, J. (2017). Epigenetic activation of WHSC1 functions as an oncogene and is associated with poor prognosis in cervical cancer. Oncology Reports, 37, 2286-2294. https://doi.org/10.3892/or.2017.5463
MLA
Yin, Z., Sun, Y., Ge, S., Sun, J."Epigenetic activation of WHSC1 functions as an oncogene and is associated with poor prognosis in cervical cancer". Oncology Reports 37.4 (2017): 2286-2294.
Chicago
Yin, Z., Sun, Y., Ge, S., Sun, J."Epigenetic activation of WHSC1 functions as an oncogene and is associated with poor prognosis in cervical cancer". Oncology Reports 37, no. 4 (2017): 2286-2294. https://doi.org/10.3892/or.2017.5463