Abstract
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.
Highlights
Epstein–Barr virus (EBV) antibodies and EBV-DNA serves as a useful tools for the diagnosis in Nasopharyngeal carcinoma (NPC).[7,8,9] there have been improvements in diagnosis techniques, irradiation and chemo-radiotherapy, local recurrence or distant metastasis are the main reasons for treatment failure.[10]
The far upstream element (FUSE)-binding proteins (FBPs) are a family of three regulatory proteins, termed FUSE-binding protein 1 (FBP1), FBP2 and FBP3.21 FBP1 was first identified as a DNA-binding protein that regulates the expression of c-Myc by binding to a single-stranded FUSE located upstream of the c-Myc promoter[22,23] FBP1 is an RNA-binding protein that binds to the Hepatitis C and Enterovirus 71 RNAs and mediates their replication during retroviral infection.[24,25]
To explore the expression of FBP1 in NPC cells and tissues, we first analyzed the levels of the FBP1 protein and mRNA in two non-cancerous primary human nasopharyngeal epithelial cells and 12 NPC cell lines by western blot and quantitative real-time PCR
Summary
EBV antibodies and EBV-DNA serves as a useful tools for the diagnosis in NPC.[7,8,9] there have been improvements in diagnosis techniques, irradiation and chemo-radiotherapy, local recurrence or distant metastasis are the main reasons for treatment failure.[10]. We explored the function of the FBP1 protein in NPC cells using two independent small interference RNAs (siRNAs) to knock down the expression of FBP1, and found that silencing FBP1 suppresses cell proliferation, colony-formation abilities, side populations (SPs) and markedly reduces tumorigenesis in nude mice. Taken together, these results indicate that FBP1 was overexpressed in NPC and had an important role in the development of NPC
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