Journal
ONCOTARGET
Volume 6, Issue 13, Pages 10868-10879Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3451
Keywords
microRNA; microRNA-217; EZH2; gastric cancer; metastasis
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Funding
- National High Technology Research and Development Program of China (863 Program), China [2012AA02A506]
- National Natural Science Foundation of China [81372570]
- Science and Technology Department of Guangdong Province, China [2012B031800088]
- Medical Scientific Research Foundation of Guangdong Province, China [C2011019]
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microRNA-217 (miR-217) is frequently dysregulated in cancer. Here, we report that miR-217 levels were lower in tumor tissue compared with the adjacent normal tissue. Low levels of miR-217 were associated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients. The ectopic expression of miR-217 inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas knockdown of endogenous miR-217 increased cell proliferation and invasion. Further experiments revealed that Polycomb group protein enhancer of zeste homolog 2 (EZH2) was a direct target of miR-217 in gastric cancer cells. Knockdown of EZH2 mimicked the tumor-suppressive effects of miR-217 in gastric cancer cells, whereas the reintroduction of EZH2 abolished its effects. Taken together, these results demonstrated that miR-217 may be used as a prognostic marker, and the newly identified miR-217-EZH2 axis may be a potential target in the development of therapeutic strategies for gastric cancer patients.
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