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

Abstract

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.

miR-23b-3p and miR-130a-5p affect cell growth, migration and invasion by targeting CB1R via the Wnt/β-catenin signaling pathway in gastric carcinoma

“…Numerous studies have led to the identification of various biomarkers and signaling pathways associated with the prognosis of patients with GC, including CDX2, MUC13, GP87 and COX-2. 12 – 15 A sensitive biomarker that is able to predict metastatic potential in individual cases of GC would be of clinical significance; however, no such biomarkers have been clinically applied thus far. Despite cannabinoids being associated with antineoplastic activity in a number of cancer cell types, the effect of cannabinoids on GC cells has not been clarified.…”

Association of CDX2 expression and overall survival and clinicopathologic disease manifestations in patients with gastric cancer in Northwest of Iran

“…On the other hand, CDX2 negative gastric carcinoma is associated with inactivation of P53 signaling pathway without any mutation in TP53, hence, in CDX2 negative patients with gastric cancer, P53 staining is negative. Taken together, CDX2 expression in gastric cancer CDX2 may be suggested as a useful prognostic factor for gastric cancer (21).…”

High Expression of NLRC5 is associated with prognosis of gastric cancer

“…Under long-term infection stimulation, the human organism will enter a state of chronic inflammation, which subtly induces mutations of normal cells to malignant cells and further promotes the development, invasion and metastasis of cancer cells [ 13 ]. Inflammatory factors such as ILs, TNFs, cyclooxygenase-2 and interferon-γ play important roles in the development and occurrence of GC [ 14 , 15 , 16 , 17 ]. These anti- or pro-inflammatory factors have been extensively concerned, as they can activate the natural immune system and build the first-line defense barrier against the invasion of pathogens.…”