Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang 310022, China.
Biomed Res Int. 2018 Jun 10;2018:3726091. doi: 10.1155/2018/3726091. eCollection 2018.
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.
由于 NSCLC 总体预后较差,且经常在晚期诊断,因此我们旨在本研究中寻找该疾病的新型诊断生物标志物或治疗靶点。果糖-1,6-二磷酸酶 1 (FBP1) 是糖异生的限速酶,由于启动子 DNA 序列异常甲基化,通常在 NSCLC 中丢失。临床数据表明,FBP1 基因启动子中的甲基化率与 NSCLC 患者的总生存率呈负相关。DNA 甲基转移酶抑制剂 5-aza 处理可显著增加 A549 细胞系中 mRNA 和蛋白的表达水平。另一方面,针对 FBP1 的特异性 siRNA 沉默 H460 细胞系中的 FBP1,根据 FACS 和 Transwell 测定的数据,可显著改善细胞增殖和细胞迁移。所有这些发现表明 FBP1 表达在肺癌发生和发展中的重要作用,以及检测 FBP1 启动子区域中的甲基化状态作为 NSCLC 患者预后的新型预测因子和治疗靶点的潜在用途。