How epigenetics can explain human metastasis A new role for microRNAs
How epigenetics can explain human metastasis A new role for microRNAs
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DOI：
10.4161/cc.8.3.7526
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发表时间：
2009-02-01
期刊：
影响因子：
4.3
通讯作者：
Esteller, Manel
中科院分区：
文献类型：
--
作者：
Lujambio, Amaia;Esteller, Manel
转移过程的特征在于肿瘤细胞在整个血流中扩散到远端部位，在那里这些转化的细胞增殖并产生继发性肿瘤，这是癌症患者死亡的主要原因。近年来，已经描述了大量的转移相关基因，例如钙粘蛋白、层粘连蛋白、硫酸乙酰肝素以及蛋白酶和血管生成抑制剂等。然而，这些基因在转移中改变的机制仍不清楚，因为尽管它们广泛下调，但遗传改变很少发生。表观遗传学改变，特别是CpG岛高甲基化相关沉默，可以潜在地解释许多这些基因的异常表达。组蛋白修饰剂和染色质重塑因子的破坏也有助于转移基因的改变。一类新的调节RNA，microRNA（miRNA）的成员，在癌症和转移中具有重要作用，并且在两种恶性肿瘤中也受到表观遗传机制的调节。随着我们深入了解协调所有转移步骤的表观遗传机制，我们拓宽了表观遗传药物的治疗可能性，例如DNA去甲基化药物和组蛋白去乙酰化酶抑制剂，它们可以作用于转移相关基因和miRNA，恢复它们的表达。本文就肿瘤表观遗传学和转移的最新研究进行综述，强调miRNAs及其表观遗传调控在肿瘤发生发展中的重要性。
The metastatic process is characterized by the dissemination of tumoral cells throughout the bloodstream to distal sites, where these transformed cells proliferate and give rise to secondary tumors, which are the principal cause of mortality in cancer patients. In recent years, a significant number of metastasis-related genes have been described, such as cadherins, laminins, heparan sulfates and protease and angiogenesis inhibitors, among others. However, the mechanisms by which these genes are altered in metastasis remain unclear, since genetic alterations occur rarely, despite their widespread downregulation. Epigenetic alterations, and specifically CpG island hypermethylation-associated silencing, can potentially explain the aberrant expression of many of these genes. The disruption of histone modifiers and chromatin-remodeling factors also contributes to the alteration of metastasis genes. Members of a new class of regulatory RNAs, microRNAs (miRNAs), have an important role in cancer and metastasis and are also regulated by epigenetic mechanisms in both malignancies. As we gain insight into the epigenetic mechanisms orchestrating all the metastatic steps, we broaden the therapeutic possibilities of epigenetic drugs, such as DNA demethylating drugs and histone deacetylase inhibitors, which can act upon metastasis-related genes and miRNAs, restoring their expression. In this review, the latest studies relating cancer epigenetics and metastasis are analyzed, and we emphasize the importance of miRNAs and their epigenetic regulation in tumoral progression.