miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells
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Xiaoting Jia1,*, Nan Li2,*, Cong Peng1, Yingen Deng1, Jia Wang2, Min Deng1, Minying Lu1, Jiang Yin1, Guopei Zheng1, Haiying Liu2, Zhimin He1
1Cancer Research Institute and Cancer Center of Guangzhou Medical University, Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Guangzhou 510095, Guangdong, China
2Department 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
Guopei Zheng, e-mail: [email protected]
Zhimin He, e-mail: [email protected]
Keywords: miR-493, DKK1, gastric cancer, proliferation, invasion
Received: June 11, 2015 Accepted: December 08, 2015 Published: January 20, 2016
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.
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