Autin Pierre, Blanquart Christophe, Fradin Delphine
CRCINA, INSERM, Université d'Angers, Université de Nantes, 44007 Nantes, France.
Cancers (Basel). 2019 Oct 10;11(10):1530. doi: 10.3390/cancers11101530.
Over recent decades, it has become clear that epigenetic abnormalities are involved in the hallmarks of cancer. Histone modifications, such as acetylation, play a crucial role in cancer development and progression, by regulating gene expression, such as for oncogenes or tumor suppressor genes. Therefore, histone deacetylase inhibitors (HDACi) have recently shown efficacy against both hematological and solid cancers. Designed to target histone deacetylases (HDAC), these drugs can modify the expression pattern of numerous genes including those coding for micro-RNAs (miRNA). miRNAs are small non-coding RNAs that regulate gene expression by targeting messenger RNA. Current research has found that miRNAs from a tumor can be investigated in the tumor itself, as well as in patient body fluids. In this review, we summarized current knowledge about HDAC and HDACi in several cancers, and described their impact on miRNA expression. We discuss briefly how circulating miRNAs may be used as biomarkers of HDACi response and used to investigate response to treatment.
近几十年来，表观遗传异常参与癌症特征已变得清晰。组蛋白修饰，如乙酰化，通过调节癌基因或肿瘤抑制基因等的基因表达，在癌症发生和发展中起关键作用。因此，组蛋白去乙酰化酶抑制剂（HDACi）最近已显示出对血液系统癌症和实体癌均有效。这些药物旨在靶向组蛋白去乙酰化酶（HDAC），可改变众多基因的表达模式，包括那些编码微小RNA（miRNA）的基因。miRNA是通过靶向信使RNA来调节基因表达的小非编码RNA。当前研究发现，肿瘤中的miRNA可在肿瘤本身以及患者体液中进行研究。在本综述中，我们总结了目前关于HDAC和HDACi在几种癌症中的知识，并描述了它们对miRNA表达的影响。我们简要讨论了循环miRNA如何用作HDACi反应的生物标志物以及用于研究治疗反应。
