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阴阳 1(YY1)在多药耐药()基因转录调控中的作用。

Role of Yin Yang-1 (YY1) in the transcription regulation of the multi-drug resistance () gene.

机构信息

a Unidad de Investigación en Enfermedades Oncológicas , Hospital Infantil de México, Federico Gómez , Mexico City , Mexico.

b Facultad de Medicina , Universidad Nacional Autonoma de México , Mexico City , Mexico.

出版信息

Leuk Lymphoma. 2018 Nov;59(11):2628-2638. doi: 10.1080/10428194.2018.1448083. Epub 2018 Apr 4.

Abstract

Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (/ABCB1) gene encodes P-glycoprotein (P-gp), which plays an important role in chemoresistance; however, its transcriptional regulation remains unclear. We investigated the role of YY1 in the regulation of and its relation to ALL outcomes. Analysis of the promoter revealed four putative YY1-binding sites, which we analyzed using a reporter system and ChIP analysis. YY1 silencing resulted in the inhibition of expression and function. The clinical roles of YY1 and expression were evaluated in children with ALL. Expression of both proteins was increased in ALL patients compared to controls. We identified a positive correlation between YY1 and expression. High levels of YY1 were associated with decreased overall survival. Our results demonstrated that YY1 regulates the transcription of . Therefore, YY1 may serve as a useful prognostic and/or therapeutic target.

摘要

化疗耐药性阻碍了急性淋巴细胞白血病 (ALL) 的成功治疗。多药耐药基因 1 (/ABCB1) 编码 P 糖蛋白 (P-gp),它在化疗耐药性中发挥重要作用;然而,其转录调控仍不清楚。我们研究了 YY1 在调节 和其与 ALL 结果的关系中的作用。对 启动子的分析揭示了四个可能的 YY1 结合位点,我们使用报告系统和 ChIP 分析进行了分析。YY1 沉默导致 表达和功能受到抑制。在 ALL 患儿中评估了 YY1 和 表达的临床作用。与对照组相比,ALL 患者的两种蛋白表达均增加。我们发现 YY1 和 表达之间存在正相关。高水平的 YY1 与总生存降低相关。我们的结果表明,YY1 调节 的转录。因此,YY1 可能是一个有用的预后和/或治疗靶点。

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