EIF5A1 促进上皮性卵巢癌的增殖和进展。

EIF5A1 promotes epithelial ovarian cancer proliferation and progression.

机构信息

Department of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital of the China Welfare Institute, School of Medicine, Shanghai Jiao Tong University, 910 Hengshan Road, Shanghai 200030, China.

Department of Obstetrics and Gynecology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, 85 Wujin Road, Shanghai 200080, China.

出版信息

Biomed Pharmacother. 2018 Apr;100:168-175. doi: 10.1016/j.biopha.2018.02.016. Epub 2018 Feb 8.

DOI:10.1016/j.biopha.2018.02.016

PMID:29428664

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 EIF5A1 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.

摘要

上皮性卵巢癌 (EOC) 是最常见的妇科癌症之一，死亡率最高。我们在 54 份 EOC 组织中发现了丰富的真核翻译起始因子 5A1 (EIF5A1)，并且高水平的 EIF5A1 预示着不良的生存预后。EIF5A1 异位表达增强了 EOC 细胞的增殖、迁移和侵袭能力，而 EIF5A1 敲低则抑制了这些能力。最重要的是，GC7（N1-鸟嘌呤基-1,7-二氨基庚烷，一种 EIF5A1 脱亚胺抑制剂）可以逆转 EIF5A1 上调对 EOC 细胞增殖、迁移和侵袭的影响，而突变型 EIF5A1 质粒 [携带一个单点突变 (K50→A50)，阻止脱亚胺化] 对这些恶性行为没有影响。我们的研究结果表明，EIF5A1 是 EOC 增殖和进展的重要调节因子，是 EOC 的潜在预后标志物和治疗靶点。