Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer
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DOI:
10.1038/onc.2009.500
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发表时间:
2010-04-08
期刊:
影响因子:
8
通讯作者:
Huang, Y.
Huang, Y.
中科院分区:
医学1区
文献类型:
--
作者:
Peng, S.;Maihle, N. J.;Huang, Y.

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Lin28和Oct4在人类胚胎干细胞(ES)中高度表达,并与另外两种干细胞标记蛋白(Nanog和Sox2)一起,可以将人类体细胞转化为多能性。作为一种rna结合蛋白,Lin28的作用是刺激特定mrna亚群的翻译,并抑制一组microrna的生物发生。Oct4是维持胚胎干细胞多能性和存活所必需的转录因子。在这项研究中,我们报道在细胞系和患者肿瘤样本的分析中证实了上皮性卵巢癌(EOC)细胞亚群共表达Lin28和Oct4。我们还观察到,这些蛋白在肿瘤样品中的联合表达与晚期肿瘤分级相关。有趣的是,当使用RNA干扰在同一细胞中抑制这两种蛋白的表达时,细胞生长和存活显著降低。因此,我们提出Lin28和Oct4可能在EOC的发生和/或进展中发挥重要作用,因此可能作为EOC患者开发新治疗策略的重要分子诊断和/或治疗靶点。中华肿瘤杂志(2010)29,2153-2159;doi: 10.1038 / onc.2009.500;2010年1月25日在线发布
Lin28 and Oct4 are highly expressed in human embryonic stem (ES) cells and, along with two other stem cell marker proteins (Nanog and Sox2), together can convert human somatic cells to pluripotency. As an RNA-binding protein, Lin28 acts to stimulate the translation of a specific subset of mRNAs, and to inhibit the biogenesis of a group of microRNAs. Oct4 is a transcription factor essential for the maintenance of pluripotency and survival of ES cells. In this study, we report that a sub-population of epithelial ovarian cancer (EOC) cells co-expresses Lin28 and Oct4 as demonstrated in the analyses of both cell lines and patient tumor samples. We also observe that the combined expression of these proteins in tumor samples is correlated with advanced tumor grade. Intriguingly, when the expression of these two proteins is repressed in the same cells using RNA interference, there is significant reduction in cell growth and survival. We thus propose that Lin28 and Oct4 may have important roles in the initiation and/or progression of EOC, and consequently may serve as important molecular diagnostics and/or therapeutic targets for the development of novel treatment strategies in EOC patients. Oncogene (2010) 29, 2153-2159; doi: 10.1038/onc.2009.500; published online 25 January 2010