The up-regulation of Myb may help mediate EGCG inhibition effect on mouse lung adenocarcinoma.
The up-regulation of Myb may help mediate EGCG inhibition effect on mouse lung adenocarcinoma.
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DOI：
10.1186/s40246-016-0072-4
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发表时间：
2016-07-25
期刊：
影响因子：
4.5
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Zhou H;Manthey J;Lioutikova E;Yang W;Yoshigoe K;Yang MQ;Wang H
绿色茶多酚表没食子儿茶素没食子酸酯（EGCG）通过其抗氧化活性和结合特异性蛋白调节细胞功能而在实验研究中被证明具有抑制癌症的作用。通过计算分析和功能基因组学方法，我们以前确定了一组蛋白质编码基因和microRNA的表达显着调制响应于烟草致癌剂诱导的肺腺癌在A/J小鼠的EGCG治疗。然而，这些基因在多大程度上参与了EGCG的癌症抑制仍然不清楚。在这项研究中，我们进一步采用统计方法和文献研究来分析这些数据，并结合癌症基因组图谱（TCGA）肺腺癌数据集进行额外的数据挖掘。假设，如果一个基因介导的EGCG的癌症抑制，其表达水平的变化引起的EGCG应该是相反的发生在致癌作用，我们确定Myb和Peg 3作为主要的推定基因参与癌症抑制活性。进一步的分析表明，Myb的调节可能是通过EGCG上调的microRNA，miR-449 c-5 p介导的。虽然EGCG的作用涉及多个靶点/途径，但通过挖掘现有基因组数据集的进一步分析显示，Myb和Peg 3的上调可能是EGCG体内的关键抗癌事件。本文的在线版本（doi：10.1186/s40246-016-0072-4）包含补充材料，可供授权用户使用。
Green tea polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to inhibit cancer in experimental studies through its antioxidant activity and modulations on cellular functions by binding specific proteins. By means of computational analysis and functional genomic approaches, we previously identified a set of protein coding genes and microRNAs whose expressions were significantly modulated in response to the EGCG treatment in tobacco carcinogen-induced lung adenocarcinoma in A/J mice. However, to what degree these genes are involved in the cancer inhibition of EGCG remains unclear. In this study, we further employed statistical methods and literature research to analyze these data in combination with The Cancer Genome Atlas (TCGA) lung adenocarcinoma datasets for additional data mining. Under the assumption that, if a gene mediates EGCG’s cancer inhibition, its expression level change caused by EGCG should be opposite to what occurred in the carcinogenesis, we identified Myb and Peg3 as the primary putative genes involved in the cancer inhibitory activity. Further analysis suggested that the regulation of Myb could be mediated through an EGCG-upregulated microRNA, miR-449c-5p. Although the actions of EGCG involve multiple targets/pathways, further analysis by mining the existing genomic datasets revealed that the upregulations of Myb and Peg3 are likely the key anti-cancer events of EGCG in vivo. The online version of this article (doi:10.1186/s40246-016-0072-4) contains supplementary material, which is available to authorized users.