The microRNA expression in lymph node metastasis of gastric cancer

• 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
• Project Status: Completed(Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost : ¥3,300,000、Indirect Cost : ¥990,000); Fiscal Year 2014 : ¥910,000 (Direct Cost : ¥700,000、Indirect Cost : ¥210,000); Fiscal Year 2013 : ¥1,300,000 (Direct Cost : ¥1,000,000、Indirect Cost : ¥300,000); Fiscal Year 2012 : ¥2,080,000 (Direct Cost : ¥1,600,000、Indirect Cost : ¥480,000)
• Keywords: 胃癌 / CDX2 / マイクロRNA / 炎症発癌 / 胃癌リンパ節転移 / リンパ節転移

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.

Research Products

• [Journal Article] Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma (2018)
  • Author(s): Sakai, E., Nakayama, M., Oshima, H., Kouyama, Y., Niida, A., Fujii, S., Ochiai, A., Nakayama, K. I., Mimori, K., Suzuki, Y., Hong, C. P., Ock, C. Y., Kim, S. J. and Oshima, M.
  • Journal Title: Cancer Research Volume : in press Pages : 1283-1295
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dual inhibition of EZH2 and EZH1 sensitizes PRC2-dependent tumors to proteasome inhibition. (2017)
  • Author(s): Ola Rizq, Naoya Mimura, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Yuko Kato, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Changshan Wang, Tetsuhiro Chiba, Anqi Ma, Jian Jin, Tohru Iseki, Chiaki Nakaseko, and Atsushi Iwama
  • Journal Title: Clinical Cancer Research Volume : 23(16) Pages : 4817-4830
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] NOS2 enhances KRAS-induced lung carcinogenesis, inflammation and microRNA-21 expression (2013)
  • Author(s): Okayama H, Saito M, Oue N, Weiss JM, Stauffer J, Takenoshita S, Wiltrout RH, Hussain SP, Harris CC
  • Journal Title: International Journal of Cancer Volume : 132（1） Pages : 9-18
  • DOI: 10.1002/ijc.27644
  • Peer Reviewed
• [Presentation] 胃癌におけるCDX2遺伝子発現とその意義 (2013)
  • Author(s): 齋藤元伸、岡山洋和、隈元謙介、中村泉、大木進司、石井芳正、野水整、竹之下誠一
  • Organizer: 第85回日本胃癌学会
  • Place of Presentation: 大阪国際会議場