Implications of the Use of Eukaryotic Translation Initiation Factor 5A (eIF5A) for Prognosis and Treatment of Hepatocellular Carcinoma.
Implications of the Use of Eukaryotic Translation Initiation Factor 5A (eIF5A) for Prognosis and Treatment of Hepatocellular Carcinoma.
复制标题
DOI：
10.1155/2012/760928
复制
发表时间：
2012
影响因子：
1.8
通讯作者：
Lee NP
中科院分区：
文献类型：
--
作者：
Shek FH;Fatima S;Lee NP
肝细胞癌（HCC）是一种原发性肝脏恶性肿瘤，占总肝癌病例的大多数。缺乏治疗选择和晚期诊断是HCC死亡率高的原因。在真核生物中，信使RNA（mRNA）翻译成蛋白质是蛋白质生物合成的关键过程，其中翻译的起始涉及不同真核生物翻译起始因子（eIFs）、核糖体亚基和mRNA的相互作用。真核翻译起始因子5A（eIF 5A）是参与翻译起始的eIF之一，并且eIF 5A 2（其同种型之一）由于其所在的染色体不稳定性而在包括HCC在内的各种癌症中上调。在HCC中，eIF 5A 2表达与不良预后相关，例如肿瘤转移和静脉浸润的存在。基于eIF 5A 2的功能研究，通过短干扰RNA抑制eIF 5A 2的表达可在体外增强HCC细胞的致瘤性，而eIF 5A 2的异位表达可通过诱导上皮-间充质转化增强HCC细胞的体内和体外侵袭性。总之，eIF 5A 2是一个潜在的预后标志物，也是HCC的治疗靶点。
Hepatocellular carcinoma (HCC) is a primary liver malignancy and accounts for most of the total liver cancer cases. Lack of treatment options and late diagnosis contribute to high mortality rate of HCC. In eukaryotes, translation of messenger RNA (mRNA) to protein is a key process in protein biosynthesis in which initiation of translation involves interaction of different eukaryotic translation initiation factors (eIFs), ribosome subunits and mRNAs. Eukaryotic translation initiation factor 5A (eIF5A) is one of the eIFs involved in translation initiation and eIF5A2, one of its isoforms, is upregulated in various cancers including HCC as a result of chromosomal instability, where it resides. In HCC, eIF5A2 expression is associated with adverse prognosis such as presence of tumor metastasis and venous infiltration. Based on eIF5A2 functional studies, suppressing eIF5A2 expression by short interfering RNA alleviates the tumorigenic properties of HCC cells in vitro while ectopic expression of eIF5A2 enhances the aggressiveness of HCC cells in vivo and in vitro by inducing epithelial-mesenchymal transition. In conclusion, eIF5A2 is a potential prognostic marker as well as a therapeutic target for HCC.