Reduced microRNA-218 expression is associated with high nuclear factor kappa B activation in gastric cancer
Version of Record online: 4 NOV 2009
Copyright © 2010 American Cancer Society
Volume 116, Issue 1, pages 41–49, 1 January 2010
How to Cite
Gao, C., Zhang, Z., Liu, W., Xiao, S., Gu, W. and Lu, H. (2010), Reduced microRNA-218 expression is associated with high nuclear factor kappa B activation in gastric cancer. Cancer, 116: 41–49. doi: 10.1002/cncr.24743
- Issue online: 11 JAN 2010
- Version of Record online: 4 NOV 2009
- Manuscript Accepted: 11 MAY 2009
- Manuscript Received: 8 MAY 2009
- Manuscript Revised: 8 MAY 2009
- National Natural Science Foundation of China. Grant Numbers: 30670940, 30770112
- Helicobacter pylori; nuclear factor κB;
- epidermal growth factor receptor-coamplified and overexpressed protein;
- gastric cancer
Poor expression of microRNAs (miRs) reportedly plays an important role in gastric carcinogenesis. Large-scale microarray assays have indicated that there is significant down-regulation of miR-218 in gastric cancer. miR-218 also was decreased specifically in human papillomavirus-positive cell lines, cervical lesions, and cervical cancer tissues and in bronchial airway epithelium in smokers. However, its role in carcinogenesis remains unclear, especially in Helicobacter pylori (H. pylori)-associated gastric cancer.
miR-218 levels were evaluated in 20 noncardia gastric cancer tissues, in 10 H. pylori-infected and 8 uninfected normal gastric biopsies, and in the human gastric epithelial cancer cell line AGS using TaqMan quantitative real-time polymerase chain reaction analysis. Pre-miR-218 and anti-miR-218 inhibitors were used to examine the effects of miR-218 expression on cell proliferation and apoptosis. A luciferase reporter assay was used to examine the potential target genes and related pathways.
miR-218 expression was reduced significantly in gastric cancer tissues, in H. pylori-infected gastric mucosa, and in H. pylori-infected AGS cells. Overexpression of miR-218 inhibited cell proliferation and increased apoptosis in vitro. Epidermal growth factor receptor-coamplified and overexpressed protein (ECOP), which regulates nuclear factor kappa B (NF-κB) transcriptional activity and is associated with apoptotic response, was a direct target of miR-218. Overexpression of miR-218 also inhibited NF-κB transcriptional activation and transcription of cyclooxygenase -2, a proliferative gene regulated by NF-κB.
H. pylori infection resulted in a decrease in miR-218 expression. The down-regulation of miR-218 has the potential to increase carcinogenesis by losing control of its targets, and it may be correlated with the high transcriptional activity of NF-κB that results from H. pylori infection. Cancer 2010. © 2010 American Cancer Society.