肾母细胞瘤低表达微or -204,高表达其靶基因致癌转录因子MEIS1。

IF 1.3
Karin Koller, Martin Pichler, Karin Koch, Martina Zandl, Verena Stiegelbauer, Ivo Leuschner, Gerald Hoefler, Barbara Guertl
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引用次数: 22

摘要

通过比较几项研究,我们确定了肾母细胞瘤中转录因子PBX2(前b细胞白血病同源盒2)及其结合伙伴之一MEIS1 (Meis同源盒1)可能的失调。MEIS1的调控是复杂的,已知其表达受启动子甲基化和microRNA-204 (miR-204)结合变化的影响。因此,在我们的研究中,我们评估了MEIS1和PBX2在肾母细胞瘤中的表达以及调节MEIS1表达的因素。采用定量实时聚合酶链反应(qRT-PCR)和免疫组织化学方法检测MEIS1和PBX2信使RNA (mRNA)和蛋白水平。使用甲基化特异性PCR测定MEIS1的启动子甲基化。采用qRT-PCR检测miR-204的表达水平。21例肾母细胞瘤中有18例MEIS1 mRNA表达水平较高,26例肾母细胞瘤中有22例MEIS1 mRNA表达水平较高。与肾实质相比,MicroRNA-204在所有肾母细胞瘤中的表达均有统计学意义显著降低,但MEIS1启动子甲基化状态未发生变化。23例肾母细胞瘤中有11例PBX2 mRNA高表达,其中15例有特异性核蛋白表达。在我们的研究中,我们证实了MEIS1及其结合伙伴PBX2在大多数肾母细胞瘤中的表达。在所有研究的肾母细胞瘤中,miR-204的表达均有统计学意义上的降低,这可能表明miR-204参与了肾母细胞瘤中MEIS1的调控。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Nephroblastomas show low expression of microR-204 and high expression of its target, the oncogenic transcription factor MEIS1.

By comparing several studies we identified a possible deregulation of the transcription factors PBX2 (pre-B-cell leukemia homeobox 2) and one of its binding partners, MEIS1 (Meis homeobox 1) in nephroblastomas. The regulation of MEIS1 is complex, and its expression is known to be influenced by changes of promoter methylation and binding of microRNA-204 (miR-204). Therefore, in our study, we assessed the expression of MEIS1 and PBX2 and the factors regulating expression of MEIS1 in nephroblastomas. MEIS1 and PBX2 messenger RNA (mRNA) and protein levels were investigated by quantitative real-time-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Promoter methylation of MEIS1 was evaluated using a methylation-specific PCR assay. Expression levels of miR-204 were examined by qRT-PCR. Eighteen of 21 nephroblastomas showed a high level of MEIS1 mRNA, and 22 of 26 samples had a specific nuclear protein expression. MicroRNA-204 had a statistically significantly lower expression in all nephroblastomas investigated compared with renal parenchyma, but no change of MEIS1 promoter methylation status was noted. Eleven of 23 nephroblastomas had a high expression of PBX2 mRNA, and 15 of 23 samples had a specific nuclear protein expression was noted. In our study, we demonstrated an expression of MEIS1 and its binding partner PBX2 in most nephroblastomas. The statistically significantly lower expression of miR-204 in all nephroblastomas investigated might point to an involvement of miR-204 in the regulation of MEIS1 in nephroblastomas.

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