Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure
Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure
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DOI：
10.1016/j.mrfmmm.2006.12.006
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发表时间：
2007-06-01
影响因子：
2.3
通讯作者：
Kovalchuk, Olga
中科院分区：
文献类型：
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作者：
Pogribny, Igor P.;Tryndyak, Volodymyr P.;Kovalchuk, Olga
微小RNA（miRNAs）是小的非编码RNA分子，其作为基因表达的负调节因子起作用。它们在参与控制发育、细胞增殖、细胞凋亡和应激反应的基因的调节中起着至关重要的作用。尽管miRNA水平在肿瘤中发生了实质性改变，但它们在致癌作用中的作用，特别是在早期癌前阶段，尚未确定。在这里，我们报告说，暴露于Fisher 344大鼠他莫昔芬，一种有效的大鼠肝癌，24周导致在肝脏中的miRNA基因的表达的实质性变化。我们注意到已知的致癌miRNA，如17-92簇，miR-106 a和miR-34的显著上调。此外，我们证实了这些miRNA靶向的蛋白质表达的相应变化，这些蛋白质包括重要的细胞周期调节因子、染色质修饰因子和与癌发生有关的表达调节因子。所有这些miRNA的变化都与之前报道的成熟肿瘤（包括肝细胞癌）中的变化相对应。因此，我们的研究结果表明，miRNA的变化发生在肿瘤形成之前，而不仅仅是转化状态的结果。(c)2007 Elsevier B. V.保留所有权利。
Micro RNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. They play a crucial role in the regulation of genes involved in the control of development, cell proliferation, apoptosis, and stress response. Although miRNA levels are substantially altered in tumors, their role in carcinogenesis, specifically at the early pre-cancerous stages, has not been established. Here we report that exposure of Fisher 344 rats to tamoxifen, a potent hepatocarcinogen in rats, for 24 weeks leads to substantial changes in the expression of miRNA genes in the liver. We noted a significant up-regulation of known oncogenic miRNAs, such as the 17-92 cluster, miR-106a, and miR-34. Furthermore, we confirmed the corresponding changes in the expression of proteins targeted by these miRNAs, which include important cell cycle regulators, chromatin modifiers, and expression regulators implicated in carcinogenesis. All these miRNA changes correspond to previously reported alterations in full-fledged tumors, including hepatocellular carcinomas. Thus, our findings indicate that miRNA changes occur prior to tumor formation and are not merely a consequence of a transformed state. (c) 2007 Elsevier B.V. All rights reserved.