癌症中通过 microRNAs 对 polycomb 组复合物的协调调控。
Coordinated regulation of polycomb group complexes through microRNAs in cancer.
机构信息
Michigan Center for Translational Pathology, Ann Arbor, MI 48109, USA.
出版信息
Cancer Cell. 2011 Aug 16;20(2):187-99. doi: 10.1016/j.ccr.2011.06.016.
Abstract
Polycomb Repressive Complexes (PRC1 and PRC2)-mediated epigenetic regulation is critical for maintaining cellular homeostasis. Members of Polycomb Group (PcG) proteins including EZH2, a PRC2 component, are upregulated in various cancer types, implicating their role in tumorigenesis. Here, we have identified several microRNAs (miRNAs) that are repressed by EZH2. These miRNAs, in turn, regulate the expression of PRC1 proteins BMI1 and RING2. We found that ectopic overexpression of EZH2-regulated miRNAs attenuated cancer cell growth and invasiveness, and abrogated cancer stem cell properties. Importantly, expression analysis revealed an inverse correlation between miRNA and PRC protein levels in cell culture and prostate cancer tissues. Taken together, our data have uncovered a coordinate regulation of PRC1 and PRC2 activities that is mediated by miRNAs.
摘要
多梳抑制复合物（PRC1 和 PRC2）介导的表观遗传调控对于维持细胞内稳态至关重要。多梳蛋白（PcG）家族的成员，包括 PRC2 的组成部分 EZH2，在各种癌症类型中上调，表明它们在肿瘤发生中起作用。在这里，我们鉴定了几个受 EZH2 抑制的 microRNAs（miRNAs）。这些 miRNA 反过来又调节 PRC1 蛋白 BMI1 和 RING2 的表达。我们发现，EZH2 调节的 miRNA 的异位过表达减弱了癌细胞的生长和侵袭能力，并消除了癌症干细胞特性。重要的是，表达分析显示在细胞培养物和前列腺癌组织中 miRNA 和 PRC 蛋白水平之间存在负相关。总之，我们的数据揭示了 miRNA 介导的 PRC1 和 PRC2 活性的协调调节。
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