Journal
ONCOTARGET
Volume 6, Issue 32, Pages 32586-32601Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5309
Keywords
miR-506; EZH2; proliferation; metastasis; colon cancer
Categories
Funding
- National Natural Science Foundation of China [81360367, 81560393]
- Guangxi Natural Science Foundation [2014GXNSFBA118162]
- science and technology research projects focused on universities in Guangxi [2013ZD046]
- Guangxi Health Department [Z2013464]
- Guangxi regional high incidence of early prevention of cancer research projects Key Laboratory topic [GK2014-TKF01]
- Hunan Natural Science Foundation [08JJ5009]
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Increasing evidence reveals that aberrant expression of microRNA contributes to the development and progression of colon cancer, but the roles of microRNA-506 (miR-506) in colon cancer remain elusive. Here, we demonstrated that miR-506 was down-regulated in colon cancer tissue and cells and that miR-506 expression was inversely correlated with EZH2 expression, tumor size, lymph node invasion, TNM stage and metastasis. A high level of miR-506 identified patients with a favorable prognosis. In vitro and in vivo experiments confirmed that miR-506 inhibits the proliferation and metastasis of colon cancer, and a luciferase reporter assay confirmed that EZH2 is a direct and functional target of miR-506 via the 3' UTR of EZH2. The restoration of EZH2 expression partially reversed the proliferation and invasion of miR-506-overexpressing colon cancer cells. Moreover, we confirmed that the miR-506-EZH2 axis inhibits proliferation and metastasis by activating/suppressing specific downstream tumor-associated genes and the Wnt/beta-catenin signaling pathway. Taking together, our study sheds light on the role of miR-506 as a suppressor for tumor growth and metastasis and raises the intriguing possibility that miR-506 may serve as a new potential marker for monitoring and treating colon cancer.
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