miR-493介导的DKK1下调赋予胃癌细胞增殖、侵袭和化疗抗性。
miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells.
作者信息
Jia Xiaoting, Li Nan, Peng Cong, Deng Yingen, Wang Jia, Deng Min, Lu Minying, Yin Jiang, Zheng Guopei, Liu Haiying, He Zhimin
机构信息
Cancer Research Institute and Cancer Center of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Guangzhou 510095, Guangdong, China.
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.
出版信息
Oncotarget. 2016 Feb 9;7(6):7044-54. doi: 10.18632/oncotarget.6951.
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.
在本研究中，我们证明了胃癌患者血清和组织中DKK1水平降低。DKK1水平与胃癌的肿瘤分级、TNM分期、远处转移和淋巴结转移呈负相关。DKK1水平低的胃癌患者总生存期较差。DKK1在体外和体内均抑制胃癌细胞的增殖。DKK1还抑制胃癌细胞的侵袭，但增强其化疗敏感性。机制上，胃癌中miR-493水平升高，其直接靶向并下调DKK1表达。同样，miR-493在体外和体内均促进胃癌细胞的增殖。miR-493还促进胃癌细胞的侵袭和化疗耐药。然而，DKK1过表达逆转了miR-493对增殖、侵袭和化疗敏感性的影响。因此，我们的结果为miR-493/DKK1轴在胃癌中的作用提供了新的见解。
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