Epigenetic regulation and cancer ( Review)

被引:116
作者
Chen, Q. W. [1 ,2 ]
Zhu, X. Y. [1 ,2 ]
Li, Y. Y. [3 ]
Meng, Z. Q. [1 ,2 ]
机构
[1] Fudan Univ, Shanghai Canc Ctr, Dept Integrated Oncol, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
[3] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
关键词
epigenetics; DNA methylation; histone modification; microRNAs; cancer; ABERRANT PROMOTER METHYLATION; GLOBAL HISTONE MODIFICATIONS; MESSENGER-RNA EXPRESSION; TUMOR-SUPPRESSOR GENES; H3; LYSINE; DNA METHYLATION; BREAST-CANCER; PROSTATE-CANCER; LUNG-CANCER; CELL-PROLIFERATION;
D O I
10.3892/or.2013.2913
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epigenetics' is defined as the inheritable changes in gene expression with no alterations in DNA sequences. Epigenetics is a rapidly expanding field, and the study of epigenetic regulation in cancer is emerging. Disruption of the epigenome is a fundamental mechanism in cancer, and several epigenetic drugs have been proven to prolong survival and to be less toxic than conventional chemotherapy. Promising results from combination clinical trials with DNA methylation inhibitors and histone deacetylase inhibitors have recently been reported, and data are emerging that describe molecular determinants of clinical responses. Despite significant advances, challenges remain, including a lack of predictive markers, unclear mechanisms of response and resistance, and rare responses in solid tumors. Preclinical studies are ongoing with novel classes of agents that target various components of the epigenetic machinery. In the present review, examples of studies that demonstrate the role of epigenetic regulation in human cancers with the focus on histone modifications and DNA methylation, and the recent clinical and translational data in the epigenetics field that have potential in cancer therapy are discussed.
引用
收藏
页码:523 / 532
页数:10
相关论文
共 143 条
[1]   Epigenetic control of Hox genes during neurogenesis, development, and disease [J].
Barber, Benjamin A. ;
Rastegar, Mojgan .
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 2010, 192 (05) :261-274
[2]   High-resolution profiling of histone methylations in the human genome [J].
Barski, Artern ;
Cuddapah, Suresh ;
Cui, Kairong ;
Roh, Tae-Young ;
Schones, Dustin E. ;
Wang, Zhibin ;
Wei, Gang ;
Chepelev, Iouri ;
Zhao, Keji .
CELL, 2007, 129 (04) :823-837
[3]  
BEDFORD MT, 1987, CANCER RES, V47, P5274
[4]   Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma [J].
Berdasco, Maria ;
Ropero, Santiago ;
Setien, Fernando ;
Fraga, Mario F. ;
Lapunzina, Pablo ;
Losson, Regine ;
Alaminos, Miguel ;
Cheung, Nai-Kong ;
Rahman, Nazneen ;
Esteller, Manel .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (51) :21830-21835
[5]   The mammalian epigenome [J].
Bernstein, Bradley E. ;
Meissner, Alexander ;
Lander, Eric S. .
CELL, 2007, 128 (04) :669-681
[6]   ALL-1/MLL1, a homologue of Drosophila TRITHORAX, modifies chromatin and is directly involved in infant acute leukaemia [J].
Canaani, E ;
Nakamura, T ;
Rozovskaia, T ;
Smith, ST ;
Mori, T ;
Croce, CM ;
Mazo, A .
BRITISH JOURNAL OF CANCER, 2004, 90 (04) :756-760
[7]   Aberrations of EZH2 in Cancer [J].
Chase, Andrew ;
Cross, Nicholas C. P. .
CLINICAL CANCER RESEARCH, 2011, 17 (09) :2613-2618
[8]   Pygo2 Associates with MLL2 Histone Methyltransferase and GCN5 Histone Acetyltransferase Complexes To Augment Wnt Target Gene Expression and Breast Cancer Stem-Like Cell Expansion [J].
Chen, Jiakun ;
Luo, Qicong ;
Yuan, Yuanyang ;
Huang, Xiaoli ;
Cai, Wangyu ;
Li, Chao ;
Wei, Tongzhen ;
Zhang, Ludi ;
Yang, Meng ;
Liu, Qingfeng ;
Ye, Guodong ;
Dai, Xing ;
Li, Boan .
MOLECULAR AND CELLULAR BIOLOGY, 2010, 30 (24) :5621-5635
[9]   H3K9 Histone Methyltransferase G9a Promotes Lung Cancer Invasion and Metastasis by Silencing the Cell Adhesion Molecule Ep-CAM [J].
Chen, Min-Wei ;
Hua, Kuo-Tai ;
Kao, Hsin-Jung ;
Chi, Chia-Chun ;
Wei, Lin-Hung ;
Johansson, Gunnar ;
Shiah, Shine-Gwo ;
Chen, Pai-Sheng ;
Jeng, Yung-Ming ;
Cheng, Tsu-Yao ;
Lai, Tsung-Ching ;
Chang, Jeng-Shou ;
Jan, Yi-Hua ;
Chien, Ming-Hsien ;
Yang, Chih-Jen ;
Huang, Ming-Shyan ;
Hsiao, Michael ;
Kuo, Min-Liang .
CANCER RESEARCH, 2010, 70 (20) :7830-7840
[10]   Signaling to chromatin through histone modifications [J].
Cheung, P ;
Allis, CD ;
Sassone-Corsi, P .
CELL, 2000, 103 (02) :263-271