Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.
J Cell Biochem. 2010 Oct 15;111(3):727-34. doi: 10.1002/jcb.22762.
Elevated levels of RNA binding protein HuR were found in various human cancers. However, the mechanisms underlying HuR over-expression in cancers have not been fully elucidated. Here, we show that miR-16 acts as a novel post-transcriptional regulator for HuR. Knockdown of miR-16 increased HuR protein levels in MDA-MB-231 cells, while over-expression of pre-miR16 reduced HuR expression. Neither knockdown nor over-expression of miR-16 could alter the mRNA levels of HuR. Instead, knockdown of miR-16 increased the level of de novo synthesized HuR protein. Importantly, mechanistic studies showed that miR-16 associated with the 3'UTR of HuR, and knockdown of miR-16 markedly increased the luciferase activity of a HuR 3'UTR-containing reporter. We further demonstrate that the level of miR-16 was inversely correlated with HuR protein level in human breast carcinoma. Together, our results suggest an important role of miR-16 in regulating HuR translation and link this regulatory pathway to human breast cancer.
在各种人类癌症中发现 RNA 结合蛋白 HuR 的水平升高。然而，HuR 在癌症中过表达的机制尚未完全阐明。在这里，我们表明 miR-16 作为 HuR 的新型转录后调节剂。在 MDA-MB-231 细胞中敲低 miR-16 会增加 HuR 蛋白水平，而过表达 pre-miR16 会降低 HuR 表达。miR-16 的敲低或过表达都不能改变 HuR 的 mRNA 水平。相反，敲低 miR-16 会增加新合成的 HuR 蛋白水平。重要的是，机制研究表明 miR-16 与 HuR 的 3'UTR 结合，敲低 miR-16 会显著增加含有 HuR 3'UTR 的报告基因的荧光素酶活性。我们进一步证明，miR-16 的水平与人乳腺癌中 HuR 蛋白水平呈负相关。总之，我们的结果表明 miR-16 在调节 HuR 翻译中具有重要作用，并将这种调节途径与人类乳腺癌联系起来。
Zotero 插件