MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression
MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression
复制标题
DOI：
10.1073/pnas.0706901104
复制
发表时间：
2007-12-18
影响因子：
11.1
通讯作者：
Yang, Burton B.
中科院分区：
文献类型：
--
作者：
Lee, Daniel Y.;Deng, Zhaoqun;Yang, Burton B.
MicroRNA是一种长度为18-24 nt的单链RNA，在肿瘤的发生、发展过程中起重要作用。在这里，我们发现miR-378的表达增强了细胞存活，降低了caspase-3的活性，并促进了肿瘤生长和血管生成。蛋白质组学分析表明，在体外和体内证实的miR-378的潜在靶点融合的抑制因子（Sufu）的表达减少。当与miR-378共转染时，在腐乳中含有靶位点的荧光素酶构建体的表达被抑制。Sufu构建体的转染逆转了miR-378的作用，表明miR-378在肿瘤细胞存活中的重要作用。我们还发现miR-378靶向Fus-1。在Fus-1中含有靶位点的荧光素酶构建体的表达被miR-378抑制。还产生了具有或不具有其3' UTR的Fus-1构建体。共转染实验显示miR-378的存在抑制了Fus-1的表达。通过针对Fus-1的siRNA抑制Fus-1表达增强了细胞存活。Fus-1构建体的转染逆转了miR-378在细胞存活中的功能。我们的研究结果表明，miR-378转染通过抑制两种肿瘤抑制因子Sufu和Fus-1的表达来增强细胞存活、肿瘤生长和血管生成。
MicroRNAs are single-stranded RNA of 18-24 nt expressed enclogenously that play important roles in cancer development. Here, we show that expression of miR-378 enhances cell survival, reduces caspase-3 activity, and promotes tumor growth and angiogenesis. Proteomic analysis indicates reduced expression of suppressor of fused (Sufu), a potential target of miR-378, which was confirmed in vitro and in vivo. Expression of a luciferase construct containing the target site in Sufu was repressed when cotransfected with miR-378. Transfection of a Sufu construct reversed the effect of miR-378, suggesting an important role for miR-378 in tumor cell survival. We also discovered that miR-378targets Fus-1. Expression of luciferase constructs harboring the target sites in Fus-1 was repressed by miR-378. Fus-1 constructs with or without its 3' UTR were also generated. Cotransfection experiments showed that the presence of miR-378 repressed Fus-1 expression. Suppression of Fus-1 expression by siRNA against Fus-1 enhanced cell survival. Transfection of the Fus-1 construct reversed the function of miR-378 in cell survival. Our results suggest that miR-378 transfection enhanced cell survival, tumor growth, and angiogenesis through repression of the expression of two tumor suppressors, Sufu and Fus-1.