Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II
Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II
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DOI：
10.1016/j.ejca.2009.05.003
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发表时间：
2009-08-01
影响因子：
8.4
通讯作者：
Yu, Herbert
中科院分区：
文献类型：
--
作者：
Lu, Lingeng;Katsaros, Dionyssios;Yu, Herbert
Lin-28和lin-28B是RNA结合蛋白，可以阻断microRNA let-7的成熟并影响胚胎干细胞的分化和增殖。 Lin-28 还可能调节胰岛素样生长因子 II (IGF-II) 的表达。作为参与诱导多能干细胞（iPS）制造的多能因子之一，lin-28被认为是癌症治疗的潜在治疗靶点。为了进一步了解 lin-28 在癌症中的作用，我们分析了 lin-28 及其同源物 lin-28B 在肿瘤样本中的表达，并评估了它们与 211 名原发性上皮性卵巢癌患者的 let-7a 成熟、IGF-II 表达、疾病特征和结果的关系。分析表明，lin-28和lin-28B均与primary和pre-let-7a-3呈正相关； lin-28B（而非 lin-28）与成熟的 let-7a 呈负相关。 lin-28B 与 IGF-II 表达之间也观察到正相关，而 lin-28B 与 IGF-I 或 IGFBP-3 之间未发现关联。研究进一步证明lin-28B表达与疾病进展和死亡风险相关； lin-28B 高的患者比 lin-28B 低的患者无进展生存期和总生存期更短。这些结果似乎支持了最近体外实验的结果，表明 lin-28 阻断了 let-7a 的成熟过程。我们的研究还表明 lin-28B 可能促进卵巢癌进展并作为该疾病的不利预后标志物。 lin-28B和IGF-II之间的相关性表明生长因子可能介导lin-28B对肿瘤生长的作用。 (C) 2009 Elsevier Ltd. 保留所有权利。
Lin-28 and lin-28B are RNA-binding proteins which can block microRNA let-7 maturation and affect the differentiation and proliferation of embryonic stem cells. Lin-28 may also regulate the expression of insulin-like growth factor II (IGF-II). As one of the pluripotent factors involved in making induced pluripotent stem cells (iPS), lin-28 is considered a potential therapeutic target for cancer treatment. To further understand the role of lin-28 in cancer, we analysed the expression of lin-28 and its homologue lin-28B in tumour samples, and evaluated their associations with let-7a maturation, IGF-II expression, disease features and outcomes in 211 patients with primary epithelial ovarian cancer. The analysis showed that both lin-28 and lin-28B were positively correlated with primary and pre-let-7a-3; lin-28B, not lin-28, was inversely correlated with mature let-7a. A positive correlation was also observed between lin-28B and IGF-II expression, while no association was found between lin-28B and IGF-I or IGFBP-3. The study further demonstrated that lin-28B expression was associated with the risk of disease progression and death; patients with high lin-28B had shorter progression-free and overall survival than those with low lin-28B. These results seem to support the findings of recent in vitro experiments, showing that lin-28 blocks the process of let-7a maturation. Our study also suggests that lin-28B may promote ovarian cancer progression and serve as an unfavourable prognostic marker for the disease. The correlation between lin-28B and IGF-II indicates that the growth factor may mediate the effect of lin-28B on tumour growth. (C) 2009 Elsevier Ltd. All rights reserved.