title: Eukaryotic translation initiation factor 5A2 promotes metabolic reprogramming in hepatocellular carcinoma cells.
abstract: Reprogramming of intracellular metabolism is common in liver cancer cells. Understanding the mechanisms of cell metabolic reprogramming may present a new basis for liver cancer treatment. In our previous study, we reported that a novel oncogene eukaryotic translation initiation factor 5A2 (EIF5A2) promotes tumorigenesis under hypoxic condition. Here, we aim to investigate the role of EIF5A2 in cell metabolic reprogramming during hepatocellular carcinoma (HCC) development. In this study, we reported that the messenger RNA (mRNA) level of EIF5A2 was upregulated in 59 of 105 (56.2%) HCC clinical samples (P = 0.015), and EIF5A2 overexpression was significantly associated with shorter survival time of patients with HCC (P = 0.021). Ectopic expression of EIF5A2 in HCC cell lines significantly promoted cell growth and accelerated glucose utilization and lipogenesis rates. The high rates of glucose uptake and lactate secretion conferred by EIF5A2 revealed an abnormal activity of aerobic glycolysis in HCC cells. Several key enzymes involved in glycolysis including glucose transporter type 1 and 2, hexokinase 2, phosphofructokinase liver type, glyceraldehyde 3-phosphate dehydrogenase, pyruvate kinase M2 isoform, phosphoglycerate mutase 1 and lactate dehydrogenase A were upregulated by overexpression of EIF5A2. Moreover, EIF5A2 showed positive correlations with FASN and ACSS2, two key enzymes involved in the fatty acid de novo biosynthetic pathway, at both protein and mRNA levels in HCC. These results indicated that EIF5A2 may regulate fatty acid de novo biosynthesis by increasing the uptake of acetate. In conclusion, our findings demonstrate that EIF5A2 has a critical role in HCC cell metabolic reprogramming and may serve as a prominent novel therapeutic target for liver cancer treatment.
authors.affiliation: Department of Pharmacology, Shenzhen Key Laboratory of Translational Medicine of Tumor and Cancer Research Centre, School of Medicine, Shenzhen University, Shenzhen, China.|Department of Clinical Oncology and.|Centre for Cancer Research, University of Hong Kong, Hong Kong, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Cao
authors.affiliation: Department of Chemistry and State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Shu-Hai
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, Shenzhen Key Laboratory of Translational Medicine of Tumor and Cancer Research Centre, School of Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Chemistry and State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Chemistry and.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Che
authors.affiliation: Department of Clinical Oncology and.|Centre for Cancer Research, University of Hong Kong, Hong Kong, China.
authors.forename: Li-Yi
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Department of Clinical Oncology and.|Centre for Cancer Research, University of Hong Kong, Hong Kong, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Ming
authors.affiliation: Department of Chemistry and State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Teng-Fei
authors.initials: TF
authors.lastname: Liu
authors.affiliation: School of Biomedical Sciences, University of Hong Kong, Hong Kong, China.
authors.forename: Xu-Ming
authors.initials: XM
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, Shenzhen Key Laboratory of Translational Medicine of Tumor and Cancer Research Centre, School of Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, Shenzhen Key Laboratory of Translational Medicine of Tumor and Cancer Research Centre, School of Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Di
authors.initials: D
authors.lastname: Xiang
authors.affiliation: Wuhan University Shenzhen Research Institute, Shenzhen, China.|Department of Medical Genetics, School of Basic Medical Sciences, Wuhan University, Wuhan, China and.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Chemistry and.
authors.forename: On-Yee
authors.initials: OY
authors.lastname: Chan
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Chemistry and State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong, China, zwcai@hkbu.edu.hk gracelfu@szu.edu.cn.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Clinical Oncology and xyguan@hku.hk.|Centre for Cancer Research, University of Hong Kong, Hong Kong, China.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D014408:Biomarkers, Tumor; D005947:Glucose; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A