Significance of Methylation of FBP1 Gene in Non-Small Cell Lung Cancer.

Significance of Methylation of FBP1 Gene in Non-Small Cell Lung Cancer.
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非小细胞肺癌中FBP1基因甲基化的重要性。

DOI:
10.1155/2018/3726091
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发表时间:
2018
影响因子:
--
通讯作者:
Jianguo F
Jianguo F
中科院分区:
生物学3区
文献类型:
--
作者:
Dong Y;Huaying S;Danying W;Chihong Z;Ruibin J;Xiaojiang S;Jianguo F

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由于非小细胞肺癌总体预后较差,且多为晚期诊断,本研究旨在寻找新的诊断生物标志物或治疗靶点。果糖-1,6-二磷酸酶1(FBP1)是糖异生过程中的限速酶,在非小细胞肺癌中常因启动子DNA异常甲基化而缺失。临床资料表明,FBP1基因启动子甲基化率与NSCLC患者的总生存期呈负相关。DNA甲基化转移酶抑制剂5-aza可显著提高A549细胞的mRNA和蛋白表达水平。另一方面,利用针对FBP1的特异性siRNA沉默H460细胞中的FBP1,流式细胞仪和Transwell检测结果显示,显著提高了细胞的增殖和迁移能力。这些结果提示FBP1的表达在肺癌的发生发展中起着重要的作用,FBP1启动子区域的甲基化状态有可能成为预测NSCLC患者预后和治疗靶点的新指标。
Because NSCLC has poor overall prognosis and is frequently diagnosed at later stage, we aimed to seek novel diagnosis biomarkers or therapy target of the disease in this study. Fructose-1,6-bisphosphatase 1 (FBP1) is a rate-limiting enzyme in gluconeogenesis, which was usually lost in NSCLC due to abnormal methylation in promoter DNA sequence. The clinical data indicated that the methylation rate in FBP1 gene promoter was negatively related to the overall survival of the NSCLC patients. DNA methylation transferase inhibitor 5-aza treatment could significantly increase both expression levels of mRNA and protein in A549 cell line. On the other hand, silence of FBP1 in H460 cell line by using specific siRNA against FBP1 dramatically improved the cell proliferation and cell migration according to the date of FACS and transwell assays. All these findings implied the important roles of FBP1 expression in lung cancer development and progression and the potential use of the methylation status detected in FBP1 promoter region as a novel predictor for prognosis and therapeutic target for NSCLC patients.
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