Department of Pediatrics, Division of Hematology-Oncology, Keck School of Medicine, University of Southern California, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop #57, Los Angeles, CA 90027, USA.
Adv Exp Med Biol. 2013;754:137-48. doi: 10.1007/978-1-4419-9967-2_6.
MicroRNAs (miRNAs) are short noncoding RNAs with gene regulatory functions. It has been demonstrated that the genes encoding for miRNAs undergo the same regulatory epigenetic processes of protein coding genes. In turn, a specific subgroup of miRNAs, called epi-miRNAs, is able to directly target key enzymatic effectors of the epigenetic machinery (such as DNA methyltransferases, histone deacetylases, and polycomb genes), therefore indirectly affecting the expression of epigenetically regulated oncogenes and tumor suppressor genes. Also, several of the epigenetic drugs currently approved as anticancer agents affect the expression of miRNAs and this might explain part of their mechanism of action. This chapter focuses on the tight relationship between epigenetics and miRNAs and provides some insights on the translational implications of these findings, leading to the upcoming introduction of epigenetically related miRNAs in the treatment of cancer.
微小 RNA(miRNAs)是具有基因调控功能的短非编码 RNA。已经证明,miRNAs 的编码基因经历与蛋白质编码基因相同的调控表观遗传过程。反过来,一类特定的 miRNAs,称为 epi-miRNAs,能够直接靶向表观遗传机制的关键酶效应物(如 DNA 甲基转移酶、组蛋白去乙酰化酶和多梳基因),从而间接影响表观遗传调控的致癌基因和肿瘤抑制基因的表达。此外,目前作为抗癌药物批准的几种表观遗传药物会影响 miRNAs 的表达,这可能解释了它们部分作用机制。本章重点介绍了表观遗传学和 miRNAs 之间的紧密关系,并提供了这些发现的转化意义的一些见解,从而导致即将引入与表观遗传相关的 miRNAs 用于癌症治疗。