title: Far upstream element-binding protein 1 is a prognostic biomarker and promotes nasopharyngeal carcinoma progression.
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.
authors.affiliation: 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.|Collaborative Innovation Center of Cancer Medicine, National Institute of Biological Sciences, Beijing, China.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: J-L
authors.initials: JL
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: J-Z
authors.initials: JZ
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: A-J
authors.initials: AJ
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: M-Z
authors.initials: MZ
authors.lastname: Li
authors.affiliation: 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.
authors.forename: S-M
authors.initials: SM
authors.lastname: Yan
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Gao
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, National Institute of Biological Sciences, Beijing, China.|National Institute of Biological Sciences, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: 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.
authors.forename: M-S
authors.initials: MS
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D009368:Neoplasm Transplantation; D011379:Prognosis; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016601:RNA-Binding Proteins; D011836:Radiation Tolerance; D058985:Side-Population Cells / Q000378:metabolism; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D004265:DNA Helicases