Upregulation of miR-370 contributes to the progression of gastric carcinoma via suppression of FOXO1
Upregulation of miR-370 contributes to the progression of gastric carcinoma via suppression of FOXO1
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DOI：
10.1016/j.biopha.2013.04.014
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发表时间：
2013-07-01
影响因子：
7.5
通讯作者：
Zhang, Lei
中科院分区：
文献类型：
--
作者：
Fan, Conghai;Liu, Sheng;Zhang, Lei
FOXO 1在许多癌症中下调。然而，对潜在的机制知之甚少。在本研究中，我们报告了miR-370在胃癌细胞系和胃癌组织中的表达上调。过表达miR-370可促进胃癌细胞增殖和非贴壁依赖性生长，而沉默miR-370则相反。miR-370诱导的增殖与细胞周期蛋白依赖性激酶抑制剂p27（Kip 1）和p21（Cip 1）的下调以及细胞周期调节剂cyclin D1的上调相关。此外，我们确定FOXO 1是miR-370的功能靶标。FOXO 1与miR-370一起恢复表达强烈地消除了miR-370诱导的细胞增殖。综上所述，我们的研究结果揭示了胃癌中miR-370介导的FOXO 1抑制的新机制。(C)2013年Elsevier Masson SAS。All rights reserved.
FOXO1 is downregulated in a number of cancers. However, the underlying mechanisms are poorly understood. In this study, we report that the expression of miR-370 was upregulated in gastric cancer cell lines and gastric cancer tissues. Overexpression of miR-370 in gastric cancer cells promoted the cell proliferation and anchorage-independent growth, while silencing of miR-370 showed opposite effects. miR-370-induced proliferation was correlated with the downregulation of cyclin-dependent kinase inhibitors, p27(Kip1) and p21(Cip1), and the upregulation of the cell cycle regulator cyclin D1. Furthermore, we identified that FOXO1 is the functional target of miR-370. Restored expression of FOXO1 together with miR-370 strongly abrogated miR-370-induced cell proliferation. Taken together, our results revealed a novel mechanism of FOXO1 suppression mediated by miR-370 in gastric cancer. (C) 2013 Elsevier Masson SAS. All rights reserved.