Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
Oncogene. 2010 Apr 8;29(14):2153-9. doi: 10.1038/onc.2009.500. Epub 2010 Jan 25.
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.
Lin28 和 Oct4 在人类胚胎干细胞 (ES) 中高度表达，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 作用于刺激特定 mRNA 亚群的翻译，并抑制一组 microRNAs 的生物发生。Oct4 是维持多能性和 ES 细胞存活所必需的转录因子。在这项研究中，我们报告了上皮性卵巢癌 (EOC) 细胞的一个亚群共同表达 Lin28 和 Oct4，如细胞系和患者肿瘤样本的分析所示。我们还观察到，这些蛋白在肿瘤样本中的共同表达与晚期肿瘤分级相关。有趣的是，当使用 RNA 干扰在相同的细胞中抑制这两种蛋白的表达时，细胞生长和存活显著减少。因此，我们提出 Lin28 和 Oct4 可能在上皮性卵巢癌的发生和/或进展中起重要作用，因此可能成为上皮性卵巢癌患者开发新型治疗策略的重要分子诊断和/或治疗靶点。
