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Identification of Key Genes and Important Histone Modifications in Hepatocellular Carcinoma
Computational and Structural Biotechnology Journal ( IF 6 ) Pub Date : 2020-09-20 , DOI: 10.1016/j.csbj.2020.09.013
Yu-Xian Liu , Qian-Zhong Li , Yan-Ni Cao , Lu-Qiang Zhang

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in the world. It has been reported that HCC is closely related to the changes of histone modifications. However, finding histone modification patterns in key genes which related to HCC is still an important task. In our study, the patterns of 11 kinds of histone modifications in the promoter regions for the different types of genes were analyzed by hierarchical screening for hepatocyte (normal) cell line and HepG2 (tumor) cell line. The important histone modifications and their key modification regions in different types of genes were found. The results indicate that these important genes may play a pivotal role in the occurrence of HCC. By analyzing the differences of histone modifications and gene expression levels for these important genes between the two cell lines, we found that the signals of H3K4me3, H3K27ac, H3K9ac, and H3K4me2 in HCC are significantly stronger. The changed regions of important histone modifications in 17 key genes were also identified. For example, the H3K4me3 signals increased 150 times in regions (-1500, -500) bp and (0, 1000) bp of ARHGAP5 in tumor cell line than in normal cell line. Finally, a prognostic risk scoring model was constructed, and the effects of key genes on the prognosis of HCC were verified by the survival analysis. Our results may provide a more precise potential therapeutic targets for identifying key genes and histone modifications in HCC as new biomarkers.



中文翻译:

肝细胞癌关键基因和重要组蛋白修饰的鉴定

肝细胞癌(HCC)是世界上导致癌症死亡的主要原因之一。据报道,肝癌与组蛋白修饰的变化密切相关。然而,在与肝癌相关的关键基因中寻找组蛋白修饰模式仍然是一项重要的任务。在我们的研究中,通过分级筛选肝细胞(正常)细胞系和HepG2(肿瘤)细胞系,分析了不同类型基因的启动子区域中11种组蛋白修饰的模式。发现了重要的组蛋白修饰及其在不同类型基因中的关键修饰区域。结果表明,这些重要基因可能在肝癌的发生中起关键作用。通过分析两种细胞系之间这些重要基因的组蛋白修饰和基因表达水平的差异,我们发现HCC中的H3K4me3,H3K27ac,H3K9ac和H3K4me2信号明显更强。还确定了17个关键基因中重要组蛋白修饰的变化区域。例如,H3K4me3信号在(-1500,-500)bp和(0,1000)bp区域增加了150倍。肿瘤细胞系中的ARHGAP5高于正常细胞系。最后,建立了预后风险评分模型,并通过生存分析验证了关键基因对肝癌预后的影响。我们的结果可能为鉴定HCC中的关键基因和组蛋白修饰作为新的生物标志物提供更精确的潜在治疗靶标。

更新日期:2020-09-21
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