Cross Cancer Institute and Department of Oncology, Faculty of Medicine, University of Alberta, Edmonton, AB T6G1Z2, Canada.
Biochem Cell Biol. 2009 Oct;87(5):711-46. doi: 10.1139/O09-057.
Epigenetic programming is an important facet of biology, controlling gene expression patterns and the choice between developmental pathways. The Polycomb group proteins (PcGs) silence gene expression, allowing cells to both acquire and maintain identity. PcG silencing is important for stemness, X chromosome inactivation (XCI), genomic imprinting, and the abnormally silenced genes in cancers. Stem and cancer cells commonly share gene expression patterns, regulatory mechanisms, and signalling pathways. Many microRNA species have oncogenic or tumor suppressor activity, and disruptions in these networks are common in cancer; however, long non-coding (nc)RNA species are also important. Many of these directly guide PcG deposition and gene silencing at the HOX locus, during XCI, and in examples of genomic imprinting. Since inappropriate HOX expression and loss of genomic imprinting are hallmarks of cancer, disruption of long ncRNA-mediated PcG silencing likely has a role in oncogenesis. Aberrant silencing of coding and non-coding loci is critical for both the genesis and progression of cancers. In addition, PcGs are commonly abnormally overexpressed years prior to cancer pathology, making early PcG targeted therapy an option to reverse tumor formation, someday replacing the blunt instrument of eradication in the cancer therapy arsenal.
表观遗传编程是生物学的一个重要方面，控制着基因表达模式和发育途径之间的选择。Polycomb 组蛋白（PcG）沉默基因表达，使细胞能够获得和维持身份。PcG 沉默对于干性、X 染色体失活（XCI）、基因组印记以及癌症中异常沉默的基因非常重要。干细胞和癌细胞通常具有相似的基因表达模式、调控机制和信号通路。许多 microRNA 具有致癌或肿瘤抑制活性，这些网络的破坏在癌症中很常见；然而，长非编码（nc）RNA 也很重要。许多长 ncRNA 直接指导 PcG 在 HOX 基因座、XCI 期间以及基因组印记中的沉积和基因沉默。由于不适当的 HOX 表达和基因组印记的丧失是癌症的标志，因此长 ncRNA 介导的 PcG 沉默的破坏可能在致癌作用中发挥作用。编码和非编码基因座的异常沉默对于癌症的发生和进展至关重要。此外，PcG 通常在癌症病理学发生前多年就异常过度表达，使得早期针对 PcG 的靶向治疗成为一种逆转肿瘤形成的选择，有朝一日可能取代癌症治疗武器库中简单粗暴的消除方法。
