miR-370 的上调通过抑制 FOXO1 促进胃癌的进展。
Upregulation of miR-370 contributes to the progression of gastric carcinoma via suppression of FOXO1.
机构信息
XuZhou Children's Hospital, 18 Sudi North Road, Xuzhou, Jiangsu Province 221006, PR China.
出版信息
Biomed Pharmacother. 2013 Jul;67(6):521-6. doi: 10.1016/j.biopha.2013.04.014. Epub 2013 May 14.
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.
FOXO1 在多种癌症中下调。然而，其潜在机制尚不清楚。在这项研究中，我们报告 miR-370 的表达在胃癌细胞系和胃癌组织中上调。miR-370 在胃癌细胞中的过表达促进了细胞增殖和非锚定依赖性生长，而 miR-370 的沉默则显示出相反的效果。miR-370 诱导的增殖与细胞周期蛋白依赖性激酶抑制剂 p27(Kip1)和 p21(Cip1)的下调以及细胞周期调节剂 cyclin D1 的上调相关。此外，我们鉴定出 FOXO1 是 miR-370 的功能靶标。FOXO1 的恢复表达与 miR-370 一起强烈阻断了 miR-370 诱导的细胞增殖。总之，我们的结果揭示了 miR-370 在胃癌中介导 FOXO1 抑制的新机制。
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