CCAR1 5' UTR as a natural miRancer of miR-1254 overrides tamoxifen resistance.
CCAR1 5' UTR as a natural miRancer of miR-1254 overrides tamoxifen resistance.
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CCAR1 5' UTR 作为 miR-1254 的天然 miRancer 克服了他莫昔芬耐药性
DOI：
10.1038/cr.2016.32
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发表时间：
2016-06
期刊：
影响因子：
44.1
通讯作者：
Zhu T
中科院分区：
文献类型：
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作者：
Li G;Wu X;Qian W;Cai H;Sun X;Zhang W;Tan S;Wu Z;Qian P;Ding K;Lu X;Zhang X;Yan H;Song H;Guang S;Wu Q;Lobie PE;Shan G;Zhu T
微小RNA（miRNAs）通常与靶RNA中的非结构化的miRNAs结合位点结合，导致表达的相互抑制。在此，我们报告了miR-1254与细胞周期结构元件和凋亡调节因子1（CCAR 1）5′非翻译区（UTR）相互作用，这种相互作用增强了两种分子的稳定性。miR-1254在结合其靶点中的非结构化位点时也可以充当阻遏物。有趣的是，结构化的miR-1254靶向位点既充当功能性RNA基序传感单元，又充当增强miR-1254表达的独立RNA功能单元。化学设计的miRNA增强子，称为“miRancers”，可以稳定和增强感兴趣的miRNA的活性。我们进一步证明，CCAR 1 5′ UTR作为内源性miR-1254的天然miRancer，使他莫昔芬耐药乳腺癌细胞对他莫昔芬重新敏感。因此，我们的研究提出了一种新的miRNA功能模型，其中高度结构化的含有miRancer样基序的RNA片段或miRancer分子与miRNA特异性相互作用，导致相互稳定。
MicroRNAs (miRNAs) typically bind to unstructured miRNA-binding sites in target RNAs, leading to a mutual repression of expression. Here, we report that miR-1254 interacts with structured elements in cell cycle and apoptosis regulator 1 (CCAR1) 5′ untranslated region (UTR) and this interaction enhances the stability of both molecules. miR-1254 can also act as a repressor when binding to unstructured sites in its targets. Interestingly, structured miR-1254-targeting sites act as both a functional RNA motif-sensing unit, and an independent RNA functional unit that enhances miR-1254 expression. Artificially designed miRNA enhancers, termed “miRancers”, can stabilize and enhance the activity of miRNAs of interest. We further demonstrate that CCAR1 5′ UTR as a natural miRancer of endogenous miR-1254 re-sensitizes tamoxifen-resistant breast cancer cells to tamoxifen. Thus, our study presents a novel model of miRNA function, wherein highly structured miRancer-like motif-containing RNA fragments or miRancer molecules specifically interact with miRNAs, leading to reciprocal stabilization.
DOI：
10.1186/bcr900
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Willmarth NE;Albertson DG;Ethier SP
通讯作者：
Ethier SP