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首页> 外文期刊>British Journal of Cancer >Identification of Endoglin as an epigenetically regulated tumour-suppressor gene in lung cancer
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Identification of Endoglin as an epigenetically regulated tumour-suppressor gene in lung cancer

机译：鉴定Endoglin是肺癌中表观遗传学调控的肿瘤抑制基因

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Background: The transforming growth factor-beta (TGF- β ) pathway has been implicated in proliferation, migration and invasion of various cancers. Endoglin is a TGF- β accessory receptor that modulates signalling. We identified Endoglin as an epigenetically silenced tumour-suppressor gene in lung cancer by means of a genome-wide screening approach, then sought to characterise its effect on lung cancer progression. Methods: Methylation microarray and RNA sequencing were carried out on lung cancer cell lines. Epigenetic silencing of Endoglin was confirmed by methylation and expression analyses. An expression vector and a 20-gene expression panel were used to evaluate Endoglin function. Pyrosequencing was carried out on two independent cohorts comprising 112 and 202 NSCLC cases, respectively, and the impact of Endoglin methylation on overall survival (OS) was evaluated. Results: Methylation in the promoter region resulted in silencing of Endoglin, which could be reactivated by demethylation. Increased invasion coupled with altered EMT marker expression was observed in cell lines with an epithelial-like, but not those with a mesenchymal-like, profile when Endoglin was absent. Methylation was associated with decreased OS in stage I but not in stages II–III disease. Conclusions: We show that Endoglin is a common target of epigenetic silencing in lung cancer. We reveal a link between Endoglin silencing and EMT progression that might be associated with decreased survival in stage I disease.
机译：背景：转化生长因子-β（TGF-β）通路与多种癌症的增殖，迁移和侵袭有关。内皮糖蛋白是一种TGF-β辅助受体，可调节信号传导。我们通过全基因组筛选方法将内皮糖蛋白鉴定为肺癌中的一种表观遗传学沉默的肿瘤抑制基因，然后试图表征其对肺癌进展的影响。方法：对肺癌细胞株进行甲基化芯片和RNA测序。通过甲基化和表达分析证实了内皮糖蛋白的表观遗传沉默。表达载体和20基因表达面板用于评估内皮糖蛋白功能。焦磷酸测序分别在两个独立的队列中进行，分别包括112和202个NSCLC病例，并评估了内皮糖蛋白甲基化对总生存期（OS）的影响。结果：启动子区域的甲基化导致内皮糖蛋白沉默，可以通过去甲基化使其重新激活。在缺乏内皮糖蛋白的情况下，在具有上皮样特征的细胞系中观察到侵袭增加和EMT标记表达改变，而在没有间质样特征的细胞系中则未观察到。在第一阶段，甲基化与OS降低有关，但在第二至第三阶段疾病中却没有。结论：我们显示内皮糖蛋白是肺癌表观遗传沉默的常见靶标。我们揭示了内皮糖蛋白沉默与EMT进展之间的联系，这可能与I期疾病的存活率下降有关。

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