miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells.
miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells.
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miR-493介导的DKK1下调导致胃癌细胞增殖、侵袭和化疗耐药
DOI：
10.18632/oncotarget.6951
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发表时间：
2016-02-09
期刊：
影响因子：
--
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Jia X;Li N;Peng C;Deng Y;Wang J;Deng M;Lu M;Yin J;Zheng G;Liu H;He Z
在本研究中，我们证明，DKK 1的水平下降，在血清和组织中的GC。DKK 1水平与胃癌的肿瘤类型、TNM分期、远处转移和淋巴结转移呈负相关。DKK 1水平低的胃癌患者总体生存率低。DKK 1在体内外均能抑制胃癌细胞的增殖。DKK 1还抑制胃癌细胞的侵袭，但增强胃癌细胞的化疗敏感性。从机制上讲，miR-493水平在GC中增加，并直接靶向和下调DKK 1表达。一致的是，miR-493在体外和体内促进GC细胞的增殖。miR-493还促进GC细胞的侵袭和化疗抗性。然而，DKK 1过表达逆转了miR-493对增殖、侵袭和化疗敏感性的影响。因此，我们的研究结果为miR-493/DKK 1轴在GC中的作用提供了新的见解。
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.