Liu Z-H, Hu J-L, Liang J-Z, Zhou A-J, Li M-Z, Yan S-M, Zhang X, Gao S, Chen L, Zhong Q, Zeng M-S
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.
Cell Death Dis. 2015 Oct 15;6(10):e1920. doi: 10.1038/cddis.2015.258.
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor with tremendous invasion and metastasis capacities, and it has a high incidence in southeast Asia and southern China. Previous studies identified that far upstream element-binding protein 1 (FBP1), a transcriptional regulator of c-Myc that is one of the most frequently aberrantly expressed oncogenes in various human cancers, including NPC, is an important biomarker for many cancers. Our study aimed to investigate the expression and function of FBP1 in human NPC. Quantitative real-time RT-PCR (qRT-PCR), western blot and immunohistochemical staining (IHC) were performed in NPC cells and biopsies. Furthermore, the effect of FBP1 knockdown on cell proliferation, colony formation, side population tests and tumorigenesis in nude mice were measured by MTT, clonogenicity analysis, flow cytometry and a xenograft model, respectively. The results showed that the mRNA and protein levels of FBP1, which are positively correlated with c-Myc expression, were substantially higher in NPC than that in nasopharyngeal epithelial cells. IHC revealed that the patients with high FBP1 expression had a significantly poorer prognosis compared with the patients with low expression (P=0.020). In univariate analysis, high FBP1 and c-Myc expression predicted poorer overall survival (OS) and poorer progression-free survival. Multivariate analysis indicated that high FBP1 and c-Myc expression were independent prognostic markers. Knockdown of FBP1 reduced cell proliferation, clonogenicity and the ratio of side populations, as well as tumorigenesis in nude mice. These data indicate that FBP1 expression, which is closely correlated with c-Myc expression, is an independent prognostic factor and promotes NPC progression. Our results suggest that FBP1 can not only serve as a useful prognostic biomarker for NPC but also as a potential therapeutic target for NPC patients.
鼻咽癌(NPC)是一种具有极强侵袭和转移能力的恶性上皮性肿瘤,在东南亚和中国南方地区高发。既往研究表明,远上游元件结合蛋白1(FBP1)作为c-Myc的转录调节因子,是多种人类癌症(包括NPC)中最常异常表达的癌基因之一,是许多癌症的重要生物标志物。我们的研究旨在探讨FBP1在人鼻咽癌中的表达及功能。对NPC细胞和活检组织进行了定量实时RT-PCR(qRT-PCR)、蛋白质印迹和免疫组织化学染色(IHC)。此外,分别通过MTT、克隆形成分析、流式细胞术和异种移植模型检测了FBP1敲低对细胞增殖、集落形成、侧群细胞检测及裸鼠肿瘤发生的影响。结果显示,FBP1的mRNA和蛋白水平与c-Myc表达呈正相关,在NPC中显著高于鼻咽上皮细胞。IHC显示,FBP1高表达患者的预后明显比低表达患者差(P = 0.020)。单因素分析显示,FBP1和c-Myc高表达预示着较差的总生存期(OS)和无进展生存期。多因素分析表明,FBP1和c-Myc高表达是独立的预后标志物。敲低FBP1可降低细胞增殖、克隆形成能力和侧群细胞比例,以及裸鼠的肿瘤发生。这些数据表明,与c-Myc表达密切相关的FBP1表达是一个独立的预后因素,并促进NPC进展。我们的结果表明,FBP1不仅可作为NPC有用的预后生物标志物,也可作为NPC患者潜在的治疗靶点。