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

被引:37
作者
Jia, Xiaoting [1 ,2 ]
Li, Nan [3 ]
Peng, Cong [1 ,2 ]
Deng, Yingen [1 ,2 ]
Wang, Jia [3 ]
Deng, Min [1 ,2 ]
Lu, Minying [1 ,2 ]
Yin, Jiang [1 ,2 ]
Zheng, Guopei [1 ,2 ]
Liu, Haiying [3 ]
He, Zhimin [1 ,2 ]
机构
[1] Guangzhou Med Univ, Canc Res Inst, Guangzhou Key Lab Translat Med Malignant Tumor Tr, Guangzhou 510095, Guangdong, Peoples R China
[2] Guangzhou Med Univ, Ctr Canc, Guangzhou Key Lab Translat Med Malignant Tumor Tr, Guangzhou 510095, Guangdong, Peoples R China
[3] Guangzhou Med Univ, Dept Gastrointestinal Neoplasms Surg, Ctr Canc, Guangzhou Key Lab Translat Med Malignant Tumor Tr, Guangzhou 510095, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-493; DKK1; gastric cancer; proliferation; invasion; TUMOR-SUPPRESSOR; HEPATOCELLULAR-CARCINOMA; CLINICAL-SIGNIFICANCE; ANTAGONIST DKK1; SERUM; DICKKOPF-1; PATHWAY; GENE; OVEREXPRESSION; METASTASIS;
D O I
10.18632/oncotarget.6951
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:7044 / 7054
页数:11
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