Knockdown of RAGE inhibits growth and invasion of gastric cancer cells

  • X.C. Xu the First Affiliated Hospital of Xinjiang Medical University, China.
  • X. Abuduhadeer the First Affiliated Hospital of Xinjiang Medical University, China.
  • W.B. Zhang the First Affiliated Hospital of Xinjiang Medical University, China.
  • T. Li the First Affiliated Hospital of Xinjiang Medical University, China.
  • H. Gao the First Affiliated Hospital of Xinjiang Medical University, China.
  • Y.H. Wang | Wangyunhai007948@163.com the First Affiliated Hospital of Xinjiang Medical University, China.

Abstract

The receptor for advanced glycation endproducts (RAGE) is an oncogenic trans-membranous receptor, which is overexpressed in multiple human cancers. However, the role of RAGE in gastric cancer is still elusive. In this study, we investigated the expression and molecular mechanisms of RAGE in gastric cancer cells. Forty cases of gastric cancer and corresponding adjacent non-cancerous tissues (ANCT) were collected, and the expression of RAGE was assessed using immunohistochemistry (IHC) in biopsy samples. Furthermore, RAGE signaling was blocked by constructed recombinant small hairpin RNA lentiviral vector (Lv-shRAGE) used to transfect into human gastric cancer SGC-7901 cells. The expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase-2 (MMP-2) was detected by Real-time PCR and Western blot assays. Cell proliferative activities and invasive capability were respectively determined by MTT and Transwell assays. Cell apoptosis and cycle distribution were analyzed by flow cytometry. As a consequence, RAGE was found highly expressed in cancer tissues compared with the ANCT (70.0% vs 45.0%, P=0.039), and correlated with lymph node metastases (P=0.026). Knockdown of RAGE reduced cell proliferation and invasion of gastric cancer with decreased expression of AKT, PCNA and MMP-2, and induced cell apoptosis and cycle arrest. Altogether, upregulation of RAGE expression is associated with lymph node metastases of gastric cancer, and blockade of RAGE signaling suppresses growth and invasion of gastric cancer cells through AKT pathway, suggesting that RAGE may represent a potential therapeutic target for this aggressive malignancy.

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Author Biographies

X.C. Xu, the First Affiliated Hospital of Xinjiang Medical University
Department of Gastrointestinal Surgery
X. Abuduhadeer, the First Affiliated Hospital of Xinjiang Medical University
Department of Gastrointestinal Surgery
W.B. Zhang, the First Affiliated Hospital of Xinjiang Medical University
Department of Gastrointestinal Surgery
T. Li, the First Affiliated Hospital of Xinjiang Medical University
Department of Gastrointestinal Surgery
H. Gao, the First Affiliated Hospital of Xinjiang Medical University
Department of Gastrointestinal Surgery
Y.H. Wang, the First Affiliated Hospital of Xinjiang Medical University
Department of Gastrointestinal Surgery
Published
2013-11-18
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Original Papers
Supporting Agencies
this work is supported by Specialized Research Fund for Doctoral Program of Colleges and Universities (No. 20116517120001).
Keywords:
RAGE, gastric cancer, growth, invasion.
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How to Cite
Xu, X., Abuduhadeer, X., Zhang, W., Li, T., Gao, H., & Wang, Y. (2013). Knockdown of RAGE inhibits growth and invasion of gastric cancer cells. European Journal of Histochemistry, 57(4), e36. https://doi.org/10.4081/ejh.2013.e36