Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke
Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke
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DOI：
10.1096/fj.08-121384
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发表时间：
2009-03-01
期刊：
影响因子：
4.8
通讯作者：
De Flora, Silvio
中科院分区：
文献类型：
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作者：
Izzotti, Alberto;Calin, George A.;De Flora, Silvio
尽管microRNA在癌症研究中得到了广泛的研究，但关于它们对表面健康组织中有害物质的反应却知之甚少。我们分析了暴露于环境香烟烟雾（ECS）28天的大鼠肺中484种miRNA的表达。ECS使126个miRNAs（26.0%）下调2倍以上，24个miRNAs下调3倍以上。我们先前证明，4858个基因中的107个（2.9%）和518个蛋白中的50个（9.7%）在同一组织中被ECS上调，这与microRNA作为基因表达的负调控因子的作用一致。最显著下调的microRNA属于let-7、miR-10、miR-26、miR-30、miR-34、miR-99、miR-122、miR-123、miR-124、miR-125、miR-140、miR-145、miR-146、miR-191、miR-192、miR-219、miR-222和miR-223家族，其调节应激反应、凋亡、增殖、血管生成和基因表达。相反，转录抑制基因的抑制剂miR-294被ECS上调。啮齿动物microRNA及其人类同源物的失调有很强的平行性，这些同源物通常是从位于肺癌中缺失的脆性位点的基因转录的。已知五种ECS下调的microRNA受单核苷酸多态性的影响。因此，microRNA表达的变化是暴露于香烟烟雾后的早期事件。Izzotti，A.，Calin，G.一、阿里戈，P。，斯蒂尔，V.E.，克罗齐角M.，De植物群，S.暴露于香烟烟雾的大鼠肺中microRNA表达下调。FASEB J. 23，806-812（2009）
Although microRNAs have been investigated extensively in cancer research, little is known regarding their response to noxious agents in apparently healthy tissues. We analyzed the expression of 484 miRNAs in the lungs of rats exposed to environmental cigarette smoke (ECS) for 28 days. ECS down-regulated 126 miRNAs (26.0%) at least 2-fold and 24 miRNAs more than 3-fold. We previously demonstrated that 107 of 4858 genes (2.9%) and 50 of 518 proteins (9.7%) were up-regulated by ECS in the same tissue, which is consistent with the role of microRNAs as negative regulators of gene expression. The most remarkably down-regulated microRNAs belonged to the families of let-7, miR-10, miR-26, miR-30, miR-34, miR-99, miR-122, miR-123, miR-124, miR-125, miR-140, miR-145, miR-146, miR-191, miR-192, miR-219, miR-222, and miR-223, which regulate stress response, apoptosis, proliferation, angiogenesis, and expression of genes. In contrast, miR-294, an inhibitor of transcriptional repressor genes, was up-regulated by ECS. There was a strong parallelism in dysregulation of rodent microRNAs and their human homologues, which are often transcribed from genes localized in fragile sites deleted in lung cancer. Five ECS-down-regulated microRNAs are known to be affected by single nucleotide polymorphisms. Thus, changes in microRNA expression are an early event following exposure to cigarette smoke.-Izzotti, A., Calin, G. A., Arrigo, P., Steele, V. E., Croce, C. M., De Flora, S. Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J. 23, 806-812 (2009)