Article: A microrna contribution to aberrant ras activation in gastric cancer

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TitleA microrna contribution to aberrant ras activation in gastric cancer
AuthorsLam, EKY4
Wang, X3
Shin, VY2
Zhang, S4
Morrison, H1
Sun, J3
Ng, EKO2
Yu, J4
Jin, H3
KeywordsEzrin
Gastric cancer
MiR-204
Ras
Issue Date2011
PublisherE-Century Publishing Corporation. The Journal's web site is located at http://www.ajtr.org
CitationAmerican Journal Of Translational Research, 2011, v. 3 n. 2, p. 209-218 [How to Cite?]
AbstractOncogenic 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.
ISSN1943-8141
PubMed Central IDPMC3056566
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLam, EKY
dc.contributor.authorWang, X
dc.contributor.authorShin, VY
dc.contributor.authorZhang, S
dc.contributor.authorMorrison, H
dc.contributor.authorSun, J
dc.contributor.authorNg, EKO
dc.contributor.authorYu, J
dc.contributor.authorJin, H
dc.date.accessioned2011-07-27T01:37:11Z
dc.date.available2011-07-27T01:37:11Z
dc.date.issued2011
dc.description.abstractOncogenic 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.
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationAmerican Journal Of Translational Research, 2011, v. 3 n. 2, p. 209-218 [How to Cite?]
dc.identifier.epage218
dc.identifier.hkuros188344
dc.identifier.issn1943-8141
dc.identifier.issue2
dc.identifier.pmcidPMC3056566
dc.identifier.pmid21416062
dc.identifier.scopuseid_2-s2.0-79952921572
dc.identifier.spage209
dc.identifier.urihttp://hdl.handle.net/10722/135563
dc.identifier.volume3
dc.languageeng
dc.publisherE-Century Publishing Corporation. The Journal's web site is located at http://www.ajtr.org
dc.publisher.placeUnited States
dc.relation.ispartofAmerican Journal of Translational Research
dc.relation.referencesReferences in Scopus
dc.subjectEzrin
dc.subjectGastric cancer
dc.subjectMiR-204
dc.subjectRas
dc.titleA microrna contribution to aberrant ras activation in gastric cancer
dc.typeArticle
Author Affiliations
  1. Leibniz Institute for Age Research
  2. The University of Hong Kong
  3. Zhejiang University School of Medicine
  4. Chinese University of Hong Kong