Click Quantitative Mass Spectrometry Identifies PIWIL3 as a Mechanistic Target of RNA Interference Activator Enoxacin in Cancer Cells
Click Quantitative Mass Spectrometry Identifies PIWIL3 as a Mechanistic Target of RNA Interference Activator Enoxacin in Cancer Cells
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DOI：
10.1021/jacs.6b11751
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发表时间：
2017-02-01
影响因子：
15
通讯作者：
Xhemalce, Blerta
中科院分区：
文献类型：
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作者：
Abell, Nathan S.;Mercado, Marvin;Xhemalce, Blerta
Enoxacin 是一种小分子，可刺激 RNA 干扰 (RNAi)，并在癌症中选择性地充当生长抑制剂，但在未转化的细胞中不起作用。在这里，我们使用 alkenox（一种可点击的依诺沙星替代物）结合定量质谱法，将 PIWIL3 确定为依诺沙星的机械靶标。 PIWIL3 是 PIWI 亚家族的 Argonaute 蛋白，主要在种系中表达，并通过 piRNA 介导 RNAi。我们的结果表明，癌细胞重新表达 PIWIL3，通过 miRNA 抑制 RNAi，从而为癌症特异性靶向开辟了新的机会。
Enoxacin is a small molecule that stimulates RNA interference (RNAi) and acts as a growth inhibitor selectively in cancer but not in untransformed cells. Here, we used alkenox, a clickable enoxacin surrogate, coupled with quantitative mass spectrometry, to identify PIWIL3 as a mechanistic target of enoxacin. PIWIL3 is an Argonaute protein of the PIWI subfamily that is mainly expressed in the germline and that mediates RNAi through piRNAs. Our results suggest that cancer cells re-express PIWIL3 to repress RNAi through miRNAs and thus open a new opportunity for cancer-specific targeting.