Guo Xun, Connick Melanie C, Vanderhoof Jennifer, Ishak Mohammad-Ali, Hartley Rebecca S
Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Int J Mol Sci. 2015 Mar 30;16(4):7112-32. doi: 10.3390/ijms16047112.
RNA binding protein (RBPs) and microRNAs (miRNAs or miRs) are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR) containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC). Despite this, miR-16 and HuR do not affect the other's expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA.
RNA结合蛋白（RBPs）和微小RNA（miRNAs或miRs）是基因表达的转录后调节因子，与癌症的发生发展有关。尽管它们各自的作用已得到研究，但RBPs与miRNAs之间的相互作用仍在深入研究中。在此，我们表明，在乳腺癌细胞中，RBP HuR通过特异性结合细胞周期蛋白E1信使核糖核酸（mRNA）3'非翻译区（3'UTR）中富含U元件的区域来上调细胞周期蛋白E1。同样，miR-16依赖于其在细胞周期蛋白E1 3'UTR中的同源结合位点来抑制细胞周期蛋白E1。文献证据表明，HuR可以调节miRNA表达，并招募或解离RNA诱导沉默复合体（RISC）。尽管如此，miR-16和HuR并不影响彼此的表达水平或与细胞周期蛋白E1 3'UTR的结合。虽然HuR过表达部分阻断了miR-16对含有细胞周期蛋白E1 3'UTR的报告mRNA的抑制作用，但它并不阻断miR-16对内源性细胞周期蛋白E1 mRNA的抑制作用。相反，miR-16阻断了HuR介导的细胞周期蛋白E1上调。总体而言，我们的结果表明，miR-16可以在不影响HuR表达或与细胞周期蛋白E1 mRNA结合的情况下，推翻HuR对细胞周期蛋白E1的上调作用。
