H3K79me3在结直肠癌EMT-MET过程中的作用

Role of H3K79me3 in the EMT-MET for Colorectal Cancer

上皮-间充质转化(epithelial-mesenchymal transition,EMT)及其逆过程间充质-上皮转化(mesenchymal-epithelial transition,MET)是肿瘤转移的关键过程。以结直肠癌(colorectal cancer,CRC)转移期间在EMT和MET之间表达改变相反的基因为研究对象(即在EMT中下调然后在MET中上调的基因(E_(D)-M_(U))和在EMT中上调然后在MET中下调的基因(E_(U)-M_(D))),计算并比较了EMT-MET过程中组蛋白修饰水平和基因表达水平的变化,结果发现E_(D)-M_(U)基因启动子中的H3K79me3水平在EMT过程降低然后在MET过程升高。基于组蛋白修饰特征,使用随机森林对与EMT-MET相关的上下调基因进行了预测,结果发现H3K79me3的预测结果最好(AUC=0.974)。通过构建蛋白质相互作用网络确定了10个与转移相关的hub基因。最后,计算了hub基因启动子区组蛋白修饰水平的变化,结果表明H3K79me3可能是hub基因表达的关键调控因子。

Epithelial-mesenchymal transition(EMT)and its reverse process mesenchymal-epithelial transition(MET)play an important role in tumor metastasis.The genes whose expression changes oppositely between EMT and MET,that is,the genes that are down-regulated in EMT and then up-regulated in MET(E_(D)-M_(U))and the genes that are up-regulated in EMT and then down-regulated in MET(E_(U)-M_(D)),were mainly studied.The changes of histone modification and gene expression levels are calculated and compared during EMT-MET process,and it is found that the level of H3K79me3 in the promoters of E_(D)-M_(U) gene decreases in EMT and then increases in MET.Based on the histone modification features,the random forest is used to predict the up-and down-regulated genes associated with EMT-MET.The result shows that H3K79me3 has the best predictive performance(AUC=0.974).By constructing protein-protein interaction network,10 hub genes related to metastasis were identified.Finally,the changes of histone modification levels in the promoters of the hub genes were calculated.The result shows that H3K79me3 may be a key regulator for hub gene expression.