Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest
Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest
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DOI：
10.1016/j.febslet.2008.03.057
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发表时间：
2008-04-30
期刊：
影响因子：
3.5
通讯作者：
Zheng, Xiaofei
中科院分区：
文献类型：
--
作者：
Sun, Fang;Fu, Hanjiang;Zheng, Xiaofei
miRNA通过抑制翻译或通过靶向信使RNA（mRNA）以转录后方式降解来调节基因表达。在本研究中，我们发现miR-34 a的异位表达降低了细胞周期蛋白D1（CCND 1）和细胞周期蛋白依赖性激酶6（CDK 6）的mRNA和蛋白水平。我们还证明了miR-34 a靶向CCND 1的3 '-非翻译mRNA区域以及CDK 6，这反过来又干扰视网膜母细胞瘤的磷酸化。此外，我们发现，miR-34 a的过表达诱导A549细胞系的G1期细胞周期阻滞。综上所述，我们的数据表明，E。miR-34 a对G1期细胞周期阻滞的影响是通过下调CCND 1和CDK 6，这与miR-34 a的其他靶点相加或协同相关。(C)2008年欧洲生化学会联合会。Elsevier B. V.出版，保留所有权利。
miRNAs regulate gene expression by inhibiting translation or by targeting messenger RNA ( mRNA) for degradation in a post-transcriptional fashion. In the present study, we show that ectopic expression of miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (CDK6). We also demonstrate that miR-34a targets the 3'-untranslated mRNA region of CCND1 as well as CDK6, which in turn interferes with phosphorylation of retinoblastoma. In addition, we show that overexpression of miR-34a induces a significant G1 cell-cycle arrest in the A549 cell line. Taken together, our data suggest that the e. ects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.