MicroRNA-506 suppresses tumor proliferation and metastasis in colon cancer by directly targeting the oncogene EZH2

// Yi Zhang 1, 2, * , Changwei Lin 3, * , Guoqing Liao 1 , Sheng Liu 1 , Jie Ding 4 , Fang Tang 5 , Zhenran Wang 5 , Xingsi Liang 5 , Bo Li 5 , Yangchao Wei 5 , Qi Huang 5 , Xuan Li 5 , Bo Tang 5 1 Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 410008, PR China 2 Department of Oncological Surgery, Affiliated Hospital of Xuzhou Medical College, 221000, PR China 3 Department of Gastrointestinal Surgery, Third Xiangya Hospital, Central South University, 410008, PR China 4 Department of Gastrointestinal Surgery, Guizhou Provincial People's Hospital, 550000, PR China 5 Department of Hepatobiliary Surgery, Affiliated Hospital of Guilin Medical University, 541000, PR China * These authors have contributed equally to this work Correspondence to: Guoqing Liao, e-mail: liaoguoqing@medmail.com.cn Bo Tang, e-mail: dytangbo@163.com Keywords: miR-506, EZH2, proliferation, metastasis, colon cancer Received: March 27, 2015      Accepted: September 21, 2015      Published: October 03, 2015 ABSTRACT 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/β-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.