Abstract
Epithelial ovarian cancer (EOC) is one of the most common gynecological cancers and has the highest mortality rate thereof. We found abundant eukaryotic translation initiation factor 5A1 (EIF5A1) in 54 EOC tissues, and high EIF5A1 levels predicted poor survival. EIF5A1 ectopic expression enhanced EOC cell proliferative, migration, and invasive capabilities, while EIF5A1 knockdown suppressed them. Most importantly, GC7 (N1-guanyl-1,7-diaminoheptane, an EIF5A1 hypusination inhibitor) could reverse the effect of EIF5A1 upregulation on EOC cell proliferation, migration, and invasion and mutant type EIF5A1K50A plasmid [bearing a single point mutation (K50 → A50) that prevents hypusination] had no effects on these malignant behaviors. Our findings imply that EIF5A1 is a vital regulator of EOC proliferation and progression and is a potential prognostic marker and therapeutic target in EOC.
Keywords:
EIF5A1; Epithelial ovarian cancer; Progression; Proliferation.
Copyright © 2018 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Carcinoma, Ovarian Epithelial
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Movement / genetics*
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Cell Proliferation / drug effects
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Cell Proliferation / genetics*
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Epithelial Cells / metabolism
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Epithelial Cells / pathology*
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Eukaryotic Translation Initiation Factor 5A
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Female
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Guanine / analogs & derivatives
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Guanine / pharmacology
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Humans
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Neoplasm Invasiveness / genetics
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Neoplasm Invasiveness / pathology
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Neoplasms, Glandular and Epithelial / genetics
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Neoplasms, Glandular and Epithelial / metabolism*
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Neoplasms, Glandular and Epithelial / pathology
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism*
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Ovarian Neoplasms / pathology
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Ovary / metabolism
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Ovary / pathology*
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Peptide Initiation Factors / antagonists & inhibitors
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Peptide Initiation Factors / genetics
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Peptide Initiation Factors / metabolism*
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RNA-Binding Proteins / antagonists & inhibitors
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Up-Regulation
Substances
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N(1)-guanyl-1,7-diaminoheptane
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Peptide Initiation Factors
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RNA-Binding Proteins
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Guanine