抑癌蛋白 vigilin 通过转录后调控抑制乳腺癌中癌基因 c-fms 的表达。
Posttranscriptional suppression of proto-oncogene c-fms expression by vigilin in breast cancer.
机构信息
Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
出版信息
Mol Cell Biol. 2011 Jan;31(1):215-25. doi: 10.1128/MCB.01031-10. Epub 2010 Oct 25.
Abstract
cis-acting elements found in 3'-untranslated regions (UTRs) are regulatory signals determining mRNA stability and translational efficiency. By binding a novel non-AU-rich 69-nucleotide (nt) c-fms 3' UTR sequence, we previously identified HuR as a promoter of c-fms proto-oncogene mRNA. We now identify the 69-nt c-fms mRNA 3' UTR sequence as a cellular vigilin target through which vigilin inhibits the expression of c-fms mRNA and protein. Altering association of either vigilin or HuR with c-fms mRNA in vivo reciprocally affected mRNA association with the other protein. Mechanistic studies show that vigilin decreased c-fms mRNA stability. Furthermore, vigilin inhibited c-fms translation. Vigilin suppresses while HuR encourages cellular motility and invasion of breast cancer cells. In summary, we identified a competition for binding the 69-nt sequence, through which vigilin and HuR exert opposing effects on c-fms expression, suggesting a role for vigilin in suppression of breast cancer progression.
摘要
顺式作用元件存在于 3'-非翻译区（UTR）中，是决定 mRNA 稳定性和翻译效率的调节信号。我们之前通过结合新型非 AU 富含 69 个核苷酸（nt）的 c-fms 3'UTR 序列，鉴定 HuR 是 c-fms 原癌基因 mRNA 的启动子。现在，我们将 69nt 的 c-fms mRNA 3'UTR 序列鉴定为细胞 vigilin 的靶标，通过该靶标，vigilin 抑制 c-fms mRNA 和蛋白的表达。在体内改变 vigilin 或 HuR 与 c-fms mRNA 的结合，会反过来影响另一种蛋白与 mRNA 的结合。机制研究表明，vigilin 降低了 c-fms mRNA 的稳定性。此外，vigilin 还抑制了 c-fms 的翻译。vigilin 抑制，而 HuR 促进乳腺癌细胞的运动和侵袭。总之，我们鉴定出一个竞争结合 69nt 序列的机制，通过这个机制，vigilin 和 HuR 对 c-fms 的表达产生相反的影响，提示 vigilin 在抑制乳腺癌进展中发挥作用。
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