miR-17-92 微 RNA 簇在神经母细胞瘤中调控 TGF-β 通路的多个组分。
The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.
机构信息
Center for Medical Genetics, Ghent University Hospital, B-9000 Ghent, Belgium.
出版信息
Mol Cell. 2010 Dec 10;40(5):762-73. doi: 10.1016/j.molcel.2010.11.038.
Abstract
The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains elusive. Using SILAC and quantitative mass spectrometry, we examined the effects of activation of the miR-17-92 cluster on global protein expression in neuroblastoma (NB) cells. Our results reveal cooperation between individual miR-17-92 miRNAs and implicate miR-17-92 in multiple hallmarks of cancer, including proliferation and cell adhesion. Most importantly, we show that miR-17-92 is a potent inhibitor of TGF-β signaling. By functioning both upstream and downstream of pSMAD2, miR-17-92 activation triggers downregulation of multiple key effectors along the TGF-β signaling cascade as well as direct inhibition of TGF-β-responsive genes.
摘要
miR-17-92 微 RNA 簇在癌细胞中经常被激活，但它的靶标身份仍然难以捉摸。我们使用 SILAC 和定量质谱法研究了 miR-17-92 簇激活对神经母细胞瘤 (NB) 细胞中全局蛋白质表达的影响。我们的结果揭示了单个 miR-17-92 miRNAs 之间的合作，并暗示 miR-17-92 参与了癌症的多个特征，包括增殖和细胞黏附。最重要的是，我们表明 miR-17-92 是 TGF-β 信号的有效抑制剂。通过在 pSMAD2 的上游和下游发挥作用，miR-17-92 的激活触发了 TGF-β 信号级联中的多个关键效应物的下调，以及对 TGF-β 反应基因的直接抑制。
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