Histone Deacetylases: A Saga of Perturbed Acetylation Homeostasis in Cancer
Histone Deacetylases: A Saga of Perturbed Acetylation Homeostasis in Cancer
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DOI：
10.1369/0022155413506582
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发表时间：
2014-01-01
影响因子：
3.2
通讯作者：
Patra, Samir Kumar
中科院分区：
文献类型：
--
作者：
Parbin, Sabnam;Kar, Swayamsiddha;Patra, Samir Kumar
在当前的基因组医学时代，疾病被确定为基因表达异常模式的表现。癌症是这类疾病中最主要的例子。尽管在了解癌症发生和发展的分子机制方面取得了显著进展，但其表观遗传调控，特别是组蛋白去乙酰化，还需要进一步研究。组蛋白去乙酰化酶对肿瘤抑制基因具有抑制作用，是肿瘤基因表达调控网络中的关键成员之一。去乙酰化酶的高表达和功能破坏了组蛋白和非组蛋白靶蛋白中精细调节的乙酰化稳态。这导致与细胞增殖、分化、凋亡和其他细胞过程的调控有关的基因发生改变。此外，hdac表观遗传调控的可逆性使它们成为癌症治疗的有吸引力的靶点。本文综述了目前关于hdac在肿瘤发生和肿瘤进展中的知识，以及它们对癌症特征的贡献。本报告还简要介绍了各种检测组蛋白去乙酰化酶活性的方法，并讨论了组蛋白去乙酰化酶抑制剂作为新兴表观遗传药物治疗癌症的潜在作用。
In the current era of genomic medicine, diseases are identified as manifestations of anomalous patterns of gene expression. Cancer is the principal example among such maladies. Although remarkable progress has been achieved in the understanding of the molecular mechanisms involved in the genesis and progression of cancer, its epigenetic regulation, particularly histone deacetylation, demands further studies. Histone deacetylases (HDACs) are one of the key players in the gene expression regulation network in cancer because of their repressive role on tumor suppressor genes. Higher expression and function of deacetylases disrupt the finely tuned acetylation homeostasis in both histone and non-histone target proteins. This brings about alterations in the genes implicated in the regulation of cell proliferation, differentiation, apoptosis and other cellular processes. Moreover, the reversible nature of epigenetic modulation by HDACs makes them attractive targets for cancer remedy. This review summarizes the current knowledge of HDACs in tumorigenesis and tumor progression as well as their contribution to the hallmarks of cancer. The present report also describes briefly various assays to detect histone deacetylase activity and discusses the potential role of histone deacetylase inhibitors as emerging epigenetic drugs to cure cancer.