WIF1 was downregulated in cervical cancer due to promoter methylation

  • Ying Wang Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
  • Shifa Yuan Department of General Surgery, Hospital of Hebei Province Crop of Chinese Armed Police Force, Shijiazhuang, 050081, China
  • Jing Ma Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China https://orcid.org/0000-0003-4610-350X
  • Hong Liu Department of Gynecology Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
  • Lizhen Huang Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
  • Fengzhen Zhang Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
  • Xiaomei Wang Department of Gynecology, Zhengding Maternal and Child Health Hospital, Zhengding, China
DOI: https://doi.org/10.18388/abp.2020_6700

Abstract

Wnt inhibitory factor 1 (WIF1) is frequently downregulated in a variety of cancer due to promoter methylation. However, the methylation status of the WIF1 promoter in cervical cancer remains unclear. This study aimed to elucidate the mechanism by which WIF1 promoter methylation contributes to cervical cancer development. The expression of WIF1 in cervical cancer tissues was examined by immunohistochemistry. The methylation status of the WIF1 promoter in cervical cancer cells was detected by methylation specific PCR. WIF1 mRNA levels and protein levels were detected by PCR and Western blot analysis. We found that WIF1 expression was low in cervical cancer tissues compared to adjacent normal cervical tissues. The WIF1 promoter was methylated in the cervical cancer SiHa cell line but not in the normal cervical epithelial cell line Ect1. Correspondingly, WIF1 mRNA levels and protein levels were significantly lower in SiHa cells than in Ect1 cells. Treatment with 5-aza-2-deoxycytidine (AZA) led to the upregulation of WIF1 mRNA and protein levels in SiHa cells, but the effects were abrogated by treatment with WIF1 siRNA. In addition, AZA treatment induced apoptosis and inhibited the invasion of SiHa cells, and the effects were abrogated by WIF1 siRNA. The protein levels of survivin, c-myc and cyclinD1 were significantly lower in SiHa cells treated with AZA, but their levels were upregulated after treatment with WIF1 siRNA. In conclusion, the methylation of the WIF1 promoter leads to the downregulation of WIF1 and the activation of Wnt/β-catenin signaling in cervical cancer cells. WIF1 is a tumor suppressor that is inactivated in cervical cancer.

Published
2023-06-12
Issue
Vol. 70 No. 2 (2023)
Section
Articles

Acta Biochimica Polonica is an OpenAccess quarterly and publishes four issues a year. All contents are distributed under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY 4.0) license. Everybody may use the content following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.

Copyright for all published papers © stays with the authors.

Copyright for the journal: © Polish Biochemical Society.