The RNA-binding Protein HuR Opposes the Repression of ERBB-2 Gene Expression by MicroRNA miR-331-3p in Prostate Cancer Cells
The RNA-binding Protein HuR Opposes the Repression of ERBB-2 Gene Expression by MicroRNA miR-331-3p in Prostate Cancer Cells
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DOI：
10.1074/jbc.m111.301481
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发表时间：
2011-12-02
影响因子：
4.8
通讯作者：
Leedman, Peter J.
中科院分区：
文献类型：
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作者：
Epis, Michael R.;Barker, Andrew;Leedman, Peter J.
ERBB-2过表达与癌症的发生和进展有关，并介导其对治疗的抵抗。研究表明ERBB-2在前列腺癌（PCa）中的过度表达受转录后机制控制。我们最近证明ERBB-2 mRNA的3'-非翻译区（3'-UTR）包含两个结合microRNA miR-331-3p的特异性靶点，miR-331-3p抑制PCa细胞中ERBB-2的表达和信号传导。在这里，我们研究了位于ERBB-2 3'-UTR中远端miR-331-3p靶点附近的富u元素。HuR与这种富u元素的特异性结合促进了PCa细胞中ERBB-2的表达。我们发现HuR可以拮抗miR-331-3p对其远端ERBB-2 3'-UTR靶点的抑制作用。这些结果支持了rna结合蛋白和microrna之间的相互作用控制基因表达转录后调控的模型，并表明HuR和miR-3:31-3p都参与了在某些PCas中观察到的ERBB-2的过表达。
ERBB-2 overexpression is associated with the development and progression of cancer and mediates its resistance to therapy. It has been suggested that post-transcriptional mechanisms control the overexpression of ERBB-2 in prostate cancer (PCa). We recently demonstrated that the 3'-untranslated region (3'-UTR) of ERBB-2 mRNA contains two specific target sites for binding of the microRNA miR-331-3p and that miR-331-3p represses ERBB-2 expression and signaling in PCa cells. Here we investigate a U-rich element situated in close proximity to the distal miR-331-3p target site in the ERBB-2 3'-UTR. Specific binding of HuR to this U-rich element promotes ERBB-2 expression in PCa cells. We show that HuR antagonizes the repressive action of miR-331-3p on its distal ERBB-2 3'-UTR target site. These results support a model in which the interplay between RNA-binding proteins and microRNAs controls the post-transcriptional regulation of gene expression and suggest that both HuR and miR-3:31-3p participate in the overexpression of ERBB-2 observed in some PCas.