HuR Knockdown Changes the Oncogenic Potential of Oral Cancer Cells
HuR Knockdown Changes the Oncogenic Potential of Oral Cancer Cells
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DOI：
10.1158/1541-7786.mcr-09-0367
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发表时间：
2010-04-01
影响因子：
5.2
通讯作者：
Higashino, Fumihiro
中科院分区：
文献类型：
--
作者：
Kakuguchi, Wataru;Kitamura, Tetsuya;Higashino, Fumihiro
HuR 与富含 AU 元件的 mRNA 结合，保护它们免于快速降解。在这里，我们证明 HuR 的敲低会改变口腔癌细胞的致癌特性。口腔鳞状细胞癌细胞系 HSC-3 和 Ca9.22 比正常细胞更丰富地表达 HuR 蛋白和细胞质 AU 丰富元件 mRNA，接受 HuR 敲低。在HuR敲低的癌细胞中，与转染对照小干扰RNA的细胞相比，c-fos、c-myc和COX-2 mRNA的细胞质表达受到抑制，并且这些mRNA的半衰期比对照细胞中的对应物更短。 HuR 敲低细胞未能在软琼脂中形成集落，表明细胞已经失去了不依赖于贴壁的细胞生长的能力。此外，HuR 敲低后细胞的运动和侵袭活性显着降低。此外，在HuR敲低的癌细胞中，细胞周期相关蛋白（例如细胞周期蛋白A、细胞周期蛋白B1、细胞周期蛋白D1和细胞周期蛋白依赖性激酶1）的表达降低，并且HuR与cdk1 mRNA结合以稳定其。这些发现表明，HuR 敲低至少部分通过影响细胞周期来改变口腔癌细胞的特征，并显示出作为有效治疗方法的潜力。摩尔癌症研究中心； 8(4)； 520-8。 (C) 2010 AACR。
HuR binds to AU-rich element-containing mRNA to protect them from rapid degradation. Here, we show that knockdown of HuR changes the oncogenic properties of oral cancer cells. Oral squamous cell carcinoma cell lines, HSC-3 and Ca9.22, which express HuR protein and cytoplasmic AU-rich element mRNA more abundantly than normal cells, were subjected to HuR knockdown. In the HuR-knockdown cancer cells, the cytoplasmic expression of c-fos, c-myc, and COX-2 mRNAs was inhibited compared with those in cells that had been transfected with a control small interfering RNA, and the half-lives of these mRNAs were shorter than those of their counterparts in the control cells. HuR-knockdown cells failed to make colonies in soft agar, suggesting that the cells had lost their ability for anchorage-independent cell growth. Additionally, the motile and invasive activities of the cells decreased remarkably by HuR knockdown. Furthermore, the expression of cell cycle-related proteins, such as cyclin A, cyclin B1, cyclin D1, and cyclin-dependent kinase 1, was reduced in HuR-knockdown cancer cells, and HuR bound to cdk1 mRNA to stabilize it. These findings suggest that HuR knockdown changes the features of oral cancer cells, at least in part, by affecting their cell cycle and shows potential as an effective therapeutic approach. Mol Cancer Res; 8(4); 520-8. (C) 2010 AACR.