Polycomb group protein gene silencing, noncoding RNA, stem cells, and cancer
Polycomb group protein gene silencing, noncoding RNA, stem cells, and cancer
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DOI：
10.1139/o09-057
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发表时间：
2009-10-01
影响因子：
2.9
通讯作者：
Hendzel, Michael J.
中科院分区：
文献类型：
--
作者：
Gieni, Randall S.;Hendzel, Michael J.
表观遗传编程是生物学的一个重要方面，控制基因表达模式和发育途径之间的选择。Polycomb组蛋白（PcGs）沉默基因表达，使细胞获得并保持身份。PcG沉默对癌症的严酷性、X染色体失活（XCI）、基因组印记和异常沉默基因具有重要意义。干细胞和癌细胞具有共同的基因表达模式、调控机制和信号通路。许多microRNA物种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，长链非编码（nc）RNA物种也很重要。其中许多直接指导PcG沉积和HOX位点的基因沉默，在XCI期间，以及在基因组印迹的例子中。由于HOX不适当的表达和基因组印迹的缺失是癌症的标志，长ncrna介导的PcG沉默的破坏可能在肿瘤发生中起作用。编码和非编码位点的异常沉默对于癌症的发生和发展都是至关重要的。此外，PcG通常在癌症病理发生前几年异常过表达，这使得早期PcG靶向治疗成为逆转肿瘤形成的一种选择，有朝一日将取代癌症治疗库中生硬的根除工具。
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 sternness, 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.