共查询到20条相似文献,搜索用时 31 毫秒
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New therapeutic targets in cancer: the epigenetic connection 总被引:4,自引:0,他引:4
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Histone deacetylases and cancer 总被引:5,自引:0,他引:5
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The growing interest in cancer epigenetics is largely due to the reversible nature of epigenetic changes which tend to alter during the course of carcinogenesis. Major epigenetic changes including DNA methylation, chromatin modifications and miRNA regulation play important roles in tumorigenic process. There are several epigenetically active synthetic molecules such as DNA methyltransferase (DNMTs) and histone deacetylases (HDACs) inhibitors, which are either approved or, are under clinical trials for the treatment of various cancers. However, most of the synthetic inhibitors have shown adverse side effects, narrow in their specificity and also expensive. Hence, bioactive phytochemicals, which are widely available with lesser toxic effects, have been tested for their role in epigenetic modulatory activities in gene regulation for cancer prevention and therapy. Encouragingly, many bioactive phytochemicals potentially altered the expression of key tumor suppressor genes, tumor promoter genes and oncogenes through modulation of DNA methylation and chromatin modification in cancer. These bioactive phytochemicals either alone or in combination with other phytochemicals showed promising results against various cancers. Here, we summarize and discuss the role of some commonly investigated phytochemicals and their epigenetic targets that are of particular interest in cancer prevention and cancer therapy. 相似文献
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组蛋白乙酰化修饰在基因表达调控中的作用机制 总被引:4,自引:1,他引:3
表观遗传学是指 DNA序列变化以外的可遗传的基因表达改变,这种影响基因转录活性而不涉及DNA序列改变的基因表达调控方式称为表观转录调控,组蛋白乙酰化修饰是基因表观转录调控的重要机制.组蛋白翻译后修饰所引起的染色质结构重塑在真核生物基因表达调控中发挥着重要的作用.组蛋白乙酰化主要由组蛋白乙酰化酶 (histone acetylases, HATs) 和组蛋白去乙酰化酶( Histone deacetylases, HDACs) 催化完成,HATs 通过在组蛋白赖氨酸残基乙酰化,激活基因转录,而HDACs 使组蛋白去乙酰化,抑制基因转录.组蛋白乙酰化和去乙酰化与基因的表达调控密切相关,HATs和HDACs之间的动态平衡控制着染色质的结构和基因的表达,组蛋白乙酰化状态的失衡与肿瘤发生密切相关.最近有研究发现,肿瘤细胞的组蛋白大部分呈低乙酰化状态.组蛋白乙酰化修饰对基因表达调控及其在肿瘤发生发展中的作用具有重要意义.因此,基于细胞内组蛋白乙酰化调控机制设计开发抗肿瘤药物成为研究热点.组蛋白去乙酰化酶抑制剂可以增强细胞内组蛋白乙酰化状态,从而改变肿瘤的生物学特性,而且去乙酰化酶抑制剂作用靶点是整个基因组而不是单个基因,所以去乙酰化酶抑制剂在肿瘤治疗中具有较好的应用前景. 相似文献
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DNA demethylation and cancer: therapeutic implications 总被引:5,自引:0,他引:5
The epigenome, which is comprised of chromatin and its associated proteins and the patterns of covalent modification of DNA by methylation, sets up and maintains gene expression programs. A hallmark of cancer is a paradoxical aberration of DNA methylation patterns, a global loss of DNA methylation, that coexists with regional hypermethylation of certain genes. The hypermethylation of tumor-suppressor genes has attracted significant attention recently and DNA methylation inhibitors are being tested as potential anticancer agents. However, emerging data suggests that hypomethylation plays a role in activating genes required for metastasis and invasion. It is proposed here that hypermethylation and hypomethylation in cancer are independent processes, which target different programs at different stages in tumorigenesis. Understanding the relative roles of hypomethylation and hypermethylation in cancer has clear implications on the therapeutic use of agents targeting the DNA methylation machinery, which are discussed in this review. 相似文献
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Szyf M 《Future oncology (London, England)》2005,1(1):125-135
Cancer growth and metastasis requires reprogramming of the expression of multiple genes. The epigenome, which is comprised of chromatin and the patterns of DNA methylation, sets up and maintains gene expression programs. As expected from the broad changes in gene expression in cancer, which are characterized by both silencing and activation of multiple genes, the epigenome of cancer cells is distinguished by aberration of DNA methylation patterns, which include both hypo- and hypermethylation and aberrant regulation of DNA methylation enzymes. In contrast to genetic alterations, which are fixed and are not amenable to therapeutic intervention, pharmacological agents could alter DNA methylation patterns. This raises the prospect that DNA methylation-targeted drugs will reverse cancer growth and metastasis. One of the main challenges however, is to understand the relative role of hypo- and hypermethylation in order to achieve a balance of epigenetic therapeutic agents with positive outcome and reduced adverse effects. 相似文献
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DNA methylation and gene silencing in cancer: which is the guilty party? 总被引:12,自引:0,他引:12
The DNA methylation pattern of a cell is exquisitely controlled during early development resulting in distinct methylation patterns. The tight control of DNA methylation is released in the cancer cell characterized by a reversal of methylation states. CpG island associated genes, in particular tumour suppressor or related genes, are often hypermethylated and this is associated with silencing of these genes. Therefore methylation is commonly convicted as a critical causal event in silencing this important class of genes in cancer. In this review, we argue that methylation is not the initial guilty party in triggering gene silencing in cancer, but that methylation of CpG islands is a consequence of prior gene silencing, similar to the role of methylation in maintaining the silencing of CpG island genes on the inactive X chromosome. We propose that gene silencing is the critical precursor in cancer, as it changes the dynamic interplay between de novo methylation and demethylation of the CpG island and tilts the balance to favour hypermethylation and chromatin inactivation. 相似文献