miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells.

// Xiaoting Jia 1, * , Nan Li 2, * , Cong Peng 1 , Yingen Deng 1 , Jia Wang 2 , Min Deng 1 , Minying Lu 1 , Jiang Yin 1 , Guopei Zheng 1 , Haiying Liu 2 , Zhimin He 1 1 Cancer Research Institute and Cancer Center of Guangzhou Medical University, Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Guangzhou 510095, Guangdong, China 2 Department of Gastrointestinal Neoplasms Surgery, Cancer Center of Guangzhou Medical University, Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Guangzhou 510095, Guangdong, China * These authors contributed equally to this work Correspondence to: Guopei Zheng, e-mail: zhengguopei@126.com Zhimin He, e-mail: hezhimin2005@yahoo.com Keywords: miR-493, DKK1, gastric cancer, proliferation, invasion Received: June 11, 2015      Accepted: December 08, 2015      Published: January 20, 2016 ABSTRACT In the present study, we demonstrated that the levels of DKK1 were decreased in serums and tissues of GC. DKK1 levels inversely correlated with tumor class, TNM stage, distant metastasis and lymph node metastasis of GC. GC patients with low DKK1 levels had a poor overall survival. DKK1 inhibited the proliferation of GC cells in vitro and in vivo . DKK1 also inhibited invasion, but enhanced chemo-sensitivity of GC cells. Mechanically, miR-493 levels increased in GC and directly targeted and down-regulated DKK1 expression. In agreement, miR-493 promoted proliferation of GC cells in vitro and in vivo . MiR-493 also promoted invasion and chemo-resistance of GC cells. However, DKK1 overexpression reversed the effects of miR-493 on proliferation, invasion and chemo-sensitivity. Thus, our results provide new insight for the role of miR-493/DKK1 axis in GC.