Wnt signaling pathway upregulates DNMT1 to trigger NHERF1 promoter hypermethylation in colon cancer

  • Authors:
    • Yongli Guo
    • Meng Wang
    • Xuefeng Jia
    • Hua Zhu
    • Yaqin Zhi
    • Leilei Yuan
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  • Published online on: June 14, 2018     https://doi.org/10.3892/or.2018.6494
  • Pages: 1165-1173
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Abstract

NHERF1 is downregulated and has been identified as a new marker of colorectal cancer. However, the molecular mechanism of NHERF1 downregulation in colon cancer is not well understood. In the present study, we demonstrated that the NHERF1 mRNA level was downregulated and correlated with outcomes in colon cancer patients. NHERF1 expression was associated with EMT phenotype. High levels of promoter methylation of NHERF1 in colon cancer were observed. NHERF1 expression was restored by demethylation treatment. In addition, a negative correlation between methylation and mRNA expression of NHERF1 was observed in the TCGA dataset. Moreover, DNMT1 inhibited NHERF1 expression in vivo. DNMT1 expression was found to be negatively correlated with NHERF1 and NHERF1 expression was also restored by a DNMT1 inhibitor. DNMT1 and NHERF1 were regulated by the Wnt signaling pathway. In addition, among DNMT1 high expression patients, the Wnt signaling pathway was negatively correlated with NHERF1 expression. In contrast, among DNMT1 low expression patients, the Wnt signaling pathway was not correlated with NHERF1 expression. In conclusion, Wnt signaling increases DNMT1 expression. DNMT1 contributes to promoter hypermethylation and epigenetic NHERF1 silencing in colon cancer. In addition, we provide novel insight into the mechanisms underlying the regulation of NHERF1 expression and occurrence/progression of colon cancer.
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August-2018
Volume 40 Issue 2

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

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Spandidos Publications style
Guo Y, Wang M, Jia X, Zhu H, Zhi Y and Yuan L: Wnt signaling pathway upregulates DNMT1 to trigger NHERF1 promoter hypermethylation in colon cancer. Oncol Rep 40: 1165-1173, 2018
APA
Guo, Y., Wang, M., Jia, X., Zhu, H., Zhi, Y., & Yuan, L. (2018). Wnt signaling pathway upregulates DNMT1 to trigger NHERF1 promoter hypermethylation in colon cancer. Oncology Reports, 40, 1165-1173. https://doi.org/10.3892/or.2018.6494
MLA
Guo, Y., Wang, M., Jia, X., Zhu, H., Zhi, Y., Yuan, L."Wnt signaling pathway upregulates DNMT1 to trigger NHERF1 promoter hypermethylation in colon cancer". Oncology Reports 40.2 (2018): 1165-1173.
Chicago
Guo, Y., Wang, M., Jia, X., Zhu, H., Zhi, Y., Yuan, L."Wnt signaling pathway upregulates DNMT1 to trigger NHERF1 promoter hypermethylation in colon cancer". Oncology Reports 40, no. 2 (2018): 1165-1173. https://doi.org/10.3892/or.2018.6494