MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma.
MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma.
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DOI：
10.1371/journal.pone.0078713
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Avigad S
中科院分区：
文献类型：
--
作者：
Feinberg-Gorenshtein G;Guedj A;Shichrur K;Jeison M;Luria D;Kodman Y;Ash S;Feinmesser M;Edry L;Shomron N;Weizman A;Yaniv I;Avigad S
神经母细胞瘤（NB）起源于胚胎神经嵴，是5岁以下儿童最常见的颅外实体瘤。Dicer 1的表达降低最近被证明与NB患者的不良预后相关。本研究旨在探讨Dicer 1在神经母细胞瘤中表达下调的机制。我们使用计算预测来鉴定神经母细胞瘤中下调Dicer 1的潜在miR。预测靶向Dicer 1的miR之一是miR-192。我们使用真实的时间PCR测量了43个原发性肿瘤中miR-192的水平。在miR-192沉默后，分析dicer 1细胞活力、细胞增殖和迁移能力的水平。多变量分析将miR-192鉴定为神经母细胞瘤患者复发的独立预后标志物（p=0.04）。我们能够通过双荧光素酶测定和侧向突变分析显示，miR-192直接结合Dicer 1的3' UTR的位置1232-1238和2282-2288。在用miR-192模拟物转染的NB细胞中，细胞活力、增殖和迁移率明显增加。然而，当用miR-192抑制剂转染NB细胞时，增殖显著降低。我们认为miR-192可能通过调节Dicer 1表达而在NB中起关键作用。
Neuroblastoma (NB) arises from the embryonic neural crest and is the most common extracranial solid tumor in children under 5 years of age. Reduced expression of Dicer1 has recently been shown to be in correlation with poor prognosis in NB patients. This study aimed to investigate the mechanisms that could lead to the down-regulation of Dicer1 in neuroblastoma. We used computational prediction to identify potential miRs down-regulating Dicer1 in neuroblastoma. One of the miRs that were predicted to target Dicer1 was miR-192. We measured the levels of miR-192 in 43 primary tumors using real time PCR. Following the silencing of miR-192, the levels of dicer1 cell viability, cell proliferation and migration capability were analyzed. Multivariate analysis identified miR-192 as an independent prognostic marker for relapse in neuroblastoma patients (p=0.04). We were able to show through a dual luciferase assay and side-directed mutational analysis that miR-192 directly binds the 3' UTR of Dicer1 on positions 1232-1238 and 2282-2288. An increase in cell viability, proliferation and migration rates were evident in NB cells transfected with miR-192-mimic. Yet, there was a significant decrease in proliferation when NB cells were transfected with an miR-192-inhibitor We suggest that miR-192 might be a key player in NB by regulating Dicer1 expression.
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影响因子：
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作者：
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影响因子：
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DOI：
10.1073/pnas.0803230105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Forman, Joshua J.;Legesse-Miller, Aster;Coller, Hilary A.
通讯作者：
Coller, Hilary A.