Open Access

Activation of FXR promotes intestinal metaplasia of gastric cells via SHP‑dependent upregulation of the expression of CDX2

  • Authors:
    • Haining Zhou
    • Zhen Ni
    • Ting Li
    • Linna Su
    • Lianfeng Zhang
    • Na Liu
    • Yongquan Shi
  • View Affiliations

  • Published online on: March 23, 2018     https://doi.org/10.3892/ol.2018.8342
  • Pages: 7617-7624
  • Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric intestinal metaplasia (IM) induced by bile acid is a precancerous lesion of gastric adenocarcinoma and is associated with the expression of caudal‑related homeobox 2 (CDX2). In the present study, the role of farnesoid X receptor (FXR) on the regulation of CDX2 in gastric cells was investigated and the underlying molecular mechanisms were examined. Human gastric cell lines were treated with chenodeoxycholic acid (CDCA) or FXR agonist GW4064. Cells were treated with CDCA in the presence or absence of the FXR antagonist or FXR siRNA transfection. Next, cells were treated with CDCA in the presence or absence of SHP siRNA transfection and FXR, CDX2 and SHP mRNA and protein levels were determined by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. A chromatin immunoprecipitation assay was performed to examine the relationship between FXR and SHP and the expressions of FXR and CDX2 in gastritis and IM tissues were detected using immunohistochemistry. The results revealed that CDCA was able to induce CDX2 expression, which could be blocked by inhibition or knockdown of FXR. Mechanistically, FXR directly induced the expression of small heterodimer partner (SHP). SHP knockdown significantly decreased CDCA‑induced CDX2 expression. ChIP results indicated that FXR could directly bind SHP promoter and promote SHP ­expression. Finally, immunohistochemistry results demonstrated that the expression levels of CDX2 and FXR in human IM lesions were significantly higher, compared with those in gastritis lesions, and were positively correlated. Collectively, these results revealed that the activation of FXR and sequential direct transcriptional induction of SHP were involved in the expression of CDX2 induced by bile acid in gastric IM lesions.
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May-2018
Volume 15 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Zhou H, Ni Z, Li T, Su L, Zhang L, Liu N and Shi Y: Activation of FXR promotes intestinal metaplasia of gastric cells via SHP‑dependent upregulation of the expression of CDX2. Oncol Lett 15: 7617-7624, 2018.
APA
Zhou, H., Ni, Z., Li, T., Su, L., Zhang, L., Liu, N., & Shi, Y. (2018). Activation of FXR promotes intestinal metaplasia of gastric cells via SHP‑dependent upregulation of the expression of CDX2. Oncology Letters, 15, 7617-7624. https://doi.org/10.3892/ol.2018.8342
MLA
Zhou, H., Ni, Z., Li, T., Su, L., Zhang, L., Liu, N., Shi, Y."Activation of FXR promotes intestinal metaplasia of gastric cells via SHP‑dependent upregulation of the expression of CDX2". Oncology Letters 15.5 (2018): 7617-7624.
Chicago
Zhou, H., Ni, Z., Li, T., Su, L., Zhang, L., Liu, N., Shi, Y."Activation of FXR promotes intestinal metaplasia of gastric cells via SHP‑dependent upregulation of the expression of CDX2". Oncology Letters 15, no. 5 (2018): 7617-7624. https://doi.org/10.3892/ol.2018.8342