State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
Biochem Biophys Res Commun. 2012 Sep 14;426(1):122-8. doi: 10.1016/j.bbrc.2012.08.049. Epub 2012 Aug 16.
AU-rich elements are functional motifs in the 3'untranslated region of mRNA and are binding sites for the RNA binding protein HuR, an mRNA stabilizer and translation enhancer implicated in carcinogenesis. It is not clear whether, and, if so, how the AU-rich elements function in cells when they are separated from their mRNA and form an independent RNA species. Here, we show that a short RNA with AU-rich elements derived from C/EBPβ 3'UTR suppressed growth in a human liver cancer cell line. It specifically bound HuR, and it competed with C/EBPβ mRNA in order to bind to HuR. Our results provide evidence that the cancer cell growth suppression by this 62nt RNA containing AU-rich elements may be due to competitive binding to HuR. This work may open new options for the development of novel anti-cancer drugs.
富含 AU 的元件是 mRNA 3'非翻译区的功能基序，也是 RNA 结合蛋白 HuR 的结合位点，HuR 是一种 mRNA 稳定剂和翻译增强子，与癌症发生有关。目前尚不清楚富含 AU 的元件在与其 mRNA 分离并形成独立的 RNA 物种时，在细胞中是否发挥作用，如果发挥作用，其作用方式如何。在这里，我们表明，源自 C/EBPβ 3'UTR 的含有富含 AU 的元件的短 RNA 抑制了人肝癌细胞系的生长。它特异性地与 HuR 结合，并与 C/EBPβ mRNA 竞争以与 HuR 结合。我们的结果提供了证据，表明该含有富含 AU 的元件的 62nt RNA 通过与 HuR 竞争性结合可能抑制癌细胞生长。这项工作可能为开发新型抗癌药物开辟新的选择。
