Amodio Nicola, Rossi Marco, Raimondi Lavinia, Pitari Maria Rita, Botta Cirino, Tagliaferri Pierosandro, Tassone Pierfrancesco
Department of Experimental and Clinical Medicine, Magna Graecia University and Medical Oncology Unit, T. Campanella Cancer Center, Salvatore Venuta University Campus, Catanzaro, Italy.
Laboratory of Tissue Engineering-Innovative Technology Platforms for Tissue Engineering (PON01-00829), Rizzoli Orthopedic Institute, Palermo, Italy.
Oncotarget. 2015 May 30;6(15):12837-61. doi: 10.18632/oncotarget.3805.
A wealth of studies has highlighted the biological complexity of hematologic malignancies and the role of dysregulated signal transduction pathways. Along with the crucial role of genetic abnormalities, epigenetic aberrations are nowadays emerging as relevant players in cancer development, and significant research efforts are currently focusing on mechanisms by which histone post-translational modifications, DNA methylation and noncoding RNAs contribute to the pathobiology of cancer. As a consequence, these studies have provided the rationale for the development of epigenetic drugs, such as histone deacetylase inhibitors and demethylating compounds, some of which are currently in advanced phase of pre-clinical investigation or in clinical trials. In addition, a more recent body of evidence indicates that microRNAs (miRNAs) might target effectors of the epigenetic machinery, which are aberrantly expressed or active in cancers, thus reverting those epigenetic abnormalities driving tumor initiation and progression. This review will focus on the broad epigenetic activity triggered by members of the miR-29 family, which underlines the potential of miR-29s as candidate epi-therapeutics for the treatment of hematologic malignancies.
大量研究突出了血液系统恶性肿瘤的生物学复杂性以及信号转导通路失调的作用。除了基因异常的关键作用外,表观遗传畸变如今已成为癌症发展中的相关因素,目前大量研究工作聚焦于组蛋白翻译后修饰、DNA甲基化和非编码RNA促成癌症病理生物学的机制。因此,这些研究为表观遗传药物的开发提供了理论依据,如组蛋白脱乙酰酶抑制剂和去甲基化化合物,其中一些目前正处于临床前研究的后期阶段或临床试验阶段。此外,最近的一系列证据表明,微小RNA(miRNA)可能靶向表观遗传机制的效应物,这些效应物在癌症中异常表达或活跃,从而逆转那些驱动肿瘤起始和进展的表观遗传异常。本综述将聚焦于miR-29家族成员引发的广泛表观遗传活性,这突出了miR-29s作为治疗血液系统恶性肿瘤候选表观遗传疗法的潜力。