The microRNA expression in lymph node metastasis of gastric cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24791439
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: National Cancer Center Japan (2013-2014); Fukushima Medical University (2012)
• Principal Investigator: SAITO Motonobu 独立行政法人国立がん研究センター, 研究所, 研究員 (90611749)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 胃癌 / CDX2 / マイクロRNA / 炎症発癌

Outline of Final Research Achievements

We confirmed that decreased expression of CDX2 by immunohistochemistry was associated with poor cancer-specific survival in our 210 gastric cancer cases, consistent with several previous studies. We further investigated the mechanisms of CDX2 suppression, including the IL-6/STAT3 and p53 pathways. We confirmed that CDX2 was suppressed by activation of the IL-6/STAT3 pathway via miR-181b in vitro. We further revealed that gastric cancers, particularly those that are undifferentiated, with CDX2-negative expression are associated with p53-negative staining. The activation of the IL-6/STAT3 pathway suppressed miR-34a, which is induced by p53, suggesting that the activation of this inflammation signaling pathway suppresses the p53 pathway in tumors without TP53 mutation, resulting in poor prognostic outcome. In conclusion, the activation of the IL-6/STAT3 pathway contributes to gastric carcinogenesis through suppression of CDX2 and inactivation of p53, resulting in poor prognostic outcome.

Free Research Field

ゲノム生物