Identification of key genes and important histone modifications in hepatocellular carcinoma

被引:27
作者
Liu, Yu-Xian [1 ]
Li, Qian-Zhong [1 ,2 ]
Cao, Yan-Ni [1 ]
Zhang, Lu-Qiang [1 ]
机构
[1] Inner Mongolia Univ, Sch Phys Sci & Technol, Lab Theoret Biophys, Hohhot 010021, Peoples R China
[2] Inner Mongolia Univ, State Key Lab Reprod Regulat & Breeding Grassland, Hohhot 010070, Peoples R China
基金
中国国家自然科学基金;
关键词
Histone modification signals; Gene expression; Oncogenes; Tumor suppressor genes; Biomarkers; LIVER-CANCER; HIGH EXPRESSION; PATHWAYS; PROLIFERATION; METABOLISM; ACTIVATION; BIOMARKERS; MUTATIONS; PROGNOSIS; INVASION;
D O I
10.1016/j.csbj.2020.09.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
引用
收藏
页码:2657 / 2669
页数:13
相关论文
共 52 条
[41]   Genomics and signaling pathways in hepatocellular carcinoma [J].
Villanueva, Augusto ;
Newell, Philippa ;
Chiang, Derek Y. ;
Friedman, Scott L. ;
Llovet, Josep M. .
SEMINARS IN LIVER DISEASE, 2007, 27 (01) :55-76
[42]   HDAC1 promotes liver proliferation in young mice via interactions with C/EBPβ [J].
Wang, Guo-Li ;
Salisbury, Elizabeth ;
Shi, Xiurong ;
Timchenko, Lubov ;
Medrano, Estela E. ;
Timchenko, Nikolai A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (38) :26179-26187
[43]   Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma [J].
Wang, Kai ;
Lim, Ho Yeong ;
Shi, Stephanie ;
Lee, Jeeyun ;
Deng, Shibing ;
Xie, Tao ;
Zhu, Zhou ;
Wang, Yuli ;
Pocalyko, David ;
Yang, Wei Jennifer ;
Rejto, Paul A. ;
Mao, Mao ;
Park, Cheol-Keun ;
Xu, Jiangchun .
HEPATOLOGY, 2013, 58 (02) :706-717
[44]   The Long Noncoding RNA IncTCF7 Promotes Self-Renewal of Human Liver Cancer Stem Cells through Activation of Wnt Signaling [J].
Wang, Yanying ;
He, Lei ;
Du, Ying ;
Zhu, Pingping ;
Huang, Guanling ;
Luo, Jianjun ;
Yan, Xinlong ;
Ye, Buqing ;
Li, Chong ;
Xia, Pengyan ;
Zhang, Geng ;
Tian, Yong ;
Chen, Runsheng ;
Fan, Zusen .
CELL STEM CELL, 2015, 16 (04) :413-425
[45]  
Warnes G. R., 2009, R PACKAGE VERSION, V2, P1
[46]   Identification of Potential Driver Genes in Human Liver Carcinoma by Genomewide Screening [J].
Woo, Hyun Goo ;
Park, Eun Sung ;
Lee, Ju-Seog ;
Lee, Yun-Han ;
Ishikawa, Tsuyoshi ;
Kim, Yoon Jun ;
Thorgeirsson, Snorri S. .
CANCER RESEARCH, 2009, 69 (09) :4059-4066
[47]   Histone deacetylases function as novel potential therapeutic targets for cancer [J].
Zhang, Hui ;
Shang, Yu-Ping ;
Chen, Hong-ying ;
Li, Jun .
HEPATOLOGY RESEARCH, 2017, 47 (02) :149-159
[48]   Metascape provides a biologist-oriented resource for the analysis of systems-level datasets [J].
Zhou, Yingyao ;
Zhou, Bin ;
Pache, Lars ;
Chang, Max ;
Khodabakhshi, Alireza Hadj ;
Tanaseichuk, Olga ;
Benner, Christopher ;
Chanda, Sumit K. .
NATURE COMMUNICATIONS, 2019, 10 (1)
[49]  
Zhu Pingping, 2018, Biophys Rep, V4, P178, DOI 10.1007/s41048-018-0062-2
[50]   LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells [J].
Zhu, Pingping ;
Wang, Yanying ;
Wu, Jiayi ;
Huang, Guanling ;
Liu, Benyu ;
Ye, Buqing ;
Du, Ying ;
Gao, Guangxia ;
Tian, Yong ;
He, Lei ;
Fan, Zusen .
NATURE COMMUNICATIONS, 2016, 7