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Am J Translational Res 2011;3(2):209-218
Original Article
A microRNA contribution to aberrant Ras activation in gastric cancer
Emily KY Lam, Xian Wang, Vivian Y. Shin, Shengjie Zhang, Helen Morrison, Jie Sun, Enders KO Ng, Jun Yu,
Hongchuan Jin
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China; Biomedical Research
Center, Sir Runrun Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China; Leibniz Institute for
Age Research, Jena, Germany; Department of Surgery, The University of Hong Kong, Hong Kong, China.
Received January 20, 2011; Accepted February 5, 2011; Epub February 6, 2011; Published February 15, 2011
Abstract: Oncogenic Ras mutations are rare in gastric cancer, indicating that other mechanisms may be
responsible for aberrant Ras activation in this type of cancer. Ezrin is critical to Ras activation by remodeling
cortical actin cytoskeleton. In this study, we aimed to illustrate the relevance and regulation of ezrin in gastric
cancer. Ezrin was upregulated in gastric cancer cells. Ezrin siRNA inhibited Ras activation, cell growth and cell
migration. Ezrin overexpression was correlated with a poor outcome of gastric cancer patients (n=150, p<0.01).
Cox regression analysis revealed a significant value of ezrin expression in prognosis prediction of gastric cancer
(relative risk: 2.37, 95% confidence interval: 1.24–4.56, p<0.01). MiR-204, which was predicted to target ezrin, was
downregulated in gastric cancer cells and gastric carcinomas (n=22, p<0.01). MiR-204 inhibited ezrin expression,
Ras activation, cell growth and cell migration. Importantly, miR-204 suppressed the expression of luciferase
controlled by wild-type but not mutated ezrin 3’-UTR. In conclusion, ezrin is important to Ras activation in gastric
cancer. Its upregulation is an independent prognosis prediction factor for gastric cancer. By contributing to ezrin
upregulation, miR-204 downregulation represents a novel mechanism for aberrant Ras activation in gastric
carcinogenesis. (AJTR1101002).
Keywords: Ezrin, miR-204, Ras, gastric cancer
Full Text PDF
Address all correspondence to:
Dr. Xian Wang
Biomedical Research Center, Sir Runrun Shaw Hospital
Zhejiang University, Hangzhou, China.
Tel: +86 571 86006927; Fax: +86 571 86006145
E-mail: wangx118@yahoo.com
Dr. Hongchuan Jin
Biomedical Research Center, Sir Runrun Shaw Hospital
Zhejiang University, Hangzhou, China.
Tel: +86 571 86006366; Fax: +86 571 86006145
E-mail: jinhc@srrsh.com
Original Article
A microRNA contribution to aberrant Ras activation in gastric cancer
Emily KY Lam, Xian Wang, Vivian Y. Shin, Shengjie Zhang, Helen Morrison, Jie Sun, Enders KO Ng, Jun Yu,
Hongchuan Jin
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China; Biomedical Research
Center, Sir Runrun Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China; Leibniz Institute for
Age Research, Jena, Germany; Department of Surgery, The University of Hong Kong, Hong Kong, China.
Received January 20, 2011; Accepted February 5, 2011; Epub February 6, 2011; Published February 15, 2011
Abstract: Oncogenic Ras mutations are rare in gastric cancer, indicating that other mechanisms may be
responsible for aberrant Ras activation in this type of cancer. Ezrin is critical to Ras activation by remodeling
cortical actin cytoskeleton. In this study, we aimed to illustrate the relevance and regulation of ezrin in gastric
cancer. Ezrin was upregulated in gastric cancer cells. Ezrin siRNA inhibited Ras activation, cell growth and cell
migration. Ezrin overexpression was correlated with a poor outcome of gastric cancer patients (n=150, p<0.01).
Cox regression analysis revealed a significant value of ezrin expression in prognosis prediction of gastric cancer
(relative risk: 2.37, 95% confidence interval: 1.24–4.56, p<0.01). MiR-204, which was predicted to target ezrin, was
downregulated in gastric cancer cells and gastric carcinomas (n=22, p<0.01). MiR-204 inhibited ezrin expression,
Ras activation, cell growth and cell migration. Importantly, miR-204 suppressed the expression of luciferase
controlled by wild-type but not mutated ezrin 3’-UTR. In conclusion, ezrin is important to Ras activation in gastric
cancer. Its upregulation is an independent prognosis prediction factor for gastric cancer. By contributing to ezrin
upregulation, miR-204 downregulation represents a novel mechanism for aberrant Ras activation in gastric
carcinogenesis. (AJTR1101002).
Keywords: Ezrin, miR-204, Ras, gastric cancer
Full Text PDF
Address all correspondence to:
Dr. Xian Wang
Biomedical Research Center, Sir Runrun Shaw Hospital
Zhejiang University, Hangzhou, China.
Tel: +86 571 86006927; Fax: +86 571 86006145
E-mail: wangx118@yahoo.com
Dr. Hongchuan Jin
Biomedical Research Center, Sir Runrun Shaw Hospital
Zhejiang University, Hangzhou, China.
Tel: +86 571 86006366; Fax: +86 571 86006145
E-mail: jinhc@srrsh.com
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