CDX2 is involved in microRNA‑associated inflammatory carcinogenesis in gastric cancer

Saito,Motonobu; Okayama,Hirokazu; Saito,Katsuharu; Ando,Jin; Kumamoto,Kensuke; Nakamura,Izumi; Ohki,Shinji; Ishi,Yoshimasa; Takenoshita,Seiichi

doi:10.3892/ol.2017.6956

CDX2 is involved in microRNA‑associated inflammatory carcinogenesis in gastric cancer

Authors:
- Motonobu Saito
- Hirokazu Okayama
- Katsuharu Saito
- Jin Ando
- Kensuke Kumamoto
- Izumi Nakamura
- Shinji Ohki
- Yoshimasa Ishi
- Seiichi Takenoshita
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Affiliations: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan, Department of Surgery, Ohta Nishinouchi Hospital, 2‑5‑20 Nishinouchi, Koriyama 963‑8558, Japan
Published online on: September 15, 2017 https://doi.org/10.3892/ol.2017.6956
Pages: 6184-6190

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Abstract

The development of gastric cancer is significantly associated with chronic inflammation, such as caused by Helicobacter pylori (H. pylori) infection. Caudal‑type homeobox 2 (CDX2) is a homeobox protein involved in intestinal differentiation in normal and in aberrant locations, and is associated with inflammation. The authors of the present study have previously reported that CDX2 may have a suppressive role in the progression and carcinogenesis of gastric carcinoma. In the present study, the authors initially confirmed that a decreased expression of CDX2, as detected by immunohistochemistry, is associated with poor cancer‑specific survival in 210 gastric cancer cases, which is consistent with several previously published studies. To elucidate the potential mechanisms underlying this association, the authors investigated the mechanism of CDX2 suppression, which included interleukin (IL)‑6/signal transducer and activator of transcription 3 (STAT3) and p53 signaling pathways. The present study confirmed that CDX2 was suppressed by activation of the IL‑6/STAT3 signaling pathway via miR‑181b in vitro. It was further revealed that gastric cancer with negative CDX2 expression is associated with negative p53 staining, and this association was particularly significant in undifferentiated gastric cancer. The activation of the IL‑6/STAT3 signaling pathway suppressed miR‑34a, which is induced by p53. This suggests that the activation of the IL‑6/STAT3 signaling pathway inflammation signaling pathway suppresses the p53 signaling pathway in tumors without TP53 mutation, which results in poor prognostic outcomes. In conclusion, CDX2 may be a useful prognostic biomarker for gastric cancer and is associated with p53 inactivation.

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