MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival
MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival
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DOI：
10.1038/cdd.2010.164
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发表时间：
2011-06-01
影响因子：
12.4
通讯作者：
Westermann, F.
中科院分区：
文献类型：
--
作者：
Afanasyeva, E. A.;Mestdagh, P.;Westermann, F.
在原发性神经母细胞瘤中经常缺失的基因组区域内发现了几个microRNA（miRNA）位点，包括3p25.3处的miR-885- 5 p。在这项研究中，我们证明了miR-885- 5 p在神经母细胞瘤中3p25.3区域的缺失中下调。在神经母细胞瘤细胞系中实验性强化的miR-885- 5 p表达抑制增殖，触发细胞周期停滞、衰老和/或凋亡。miR-885- 5 p导致p53蛋白的积累并激活p53通路，导致p53靶点的上调。miR-885- 5 p表达的增强持续导致细胞周期蛋白依赖性激酶（CDK 2）和微染色体维持蛋白（MCM 5）的下调。miR-885- 5 p通过CDK 2和MCM 5的3 '-非翻译区（UTR）内的预测结合位点靶向两种基因。在神经母细胞瘤细胞中引入miR-885- 5 p后的转录谱揭示了多个基因表达的改变，包括几个p53靶基因和参与p53通路活性的许多因子。总之，这些数据提供了证据，证明miR-885- 5 p在神经母细胞瘤中具有肿瘤抑制作用，干扰细胞周期进展和细胞存活。Cell Death and Differentiation（2011）18，974-984; doi：10.1038/cdd.2010.164; 2011年1月14日在线发表
Several microRNA (miRNA) loci are found within genomic regions frequently deleted in primary neuroblastoma, including miR-885-5p at 3p25.3. In this study, we demonstrate that miR-885-5p is downregulated on loss of 3p25.3 region in neuroblastoma. Experimentally enforced miR-885-5p expression in neuroblastoma cell lines inhibits proliferation triggering cell cycle arrest, senescence and/or apoptosis. miR-885-5p leads to the accumulation of p53 protein and activates the p53 pathway, resulting in upregulation of p53 targets. Enforced miR-885-5p expression consistently leads to downregulation of cyclin-dependent kinase (CDK2) and mini-chromosome maintenance protein (MCM5). Both genes are targeted by miR-885-5p via predicted binding sites within the 3'-untranslated regions (UTRs) of CDK2 and MCM5. Transcript profiling after miR-885-5p introduction in neuroblastoma cells reveals alterations in expression of multiple genes, including several p53 target genes and a number of factors involved in p53 pathway activity. Taken together, these data provide evidence that miR-885-5p has a tumor suppressive role in neuroblastoma interfering with cell cycle progression and cell survival. Cell Death and Differentiation (2011) 18, 974-984; doi:10.1038/cdd.2010.164; published online 14 January 2011