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DNA 甲基转移酶抑制可能通过扰乱核糖体生物发生来限制癌细胞生长。

DNA methyltransferase inhibition may limit cancer cell growth by disrupting ribosome biogenesis.

机构信息

Cancer Research Centre and Dept. of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec, Canada.

出版信息

Epigenetics. 2011 Feb;6(2):128-33. doi: 10.4161/epi.6.2.13625. Epub 2011 Feb 1.

Abstract

"Mutations" in the pattern of CpG methylation imprinting of the human genome have been correlated with a number of diseases including cancer. In particular, aberrant imprinting of tumor suppressor genes by gain of CpG methylation has been observed in many cancers and thus represents an important alternative pathway to gene "mutation" and tumor progression. Inhibitors of DNA methylation display therapeutic effects in the treatment of certain cancers, and it has been assumed these effects are due to the reversal of "mutant" gene imprinting. However, significant reactivation of imprinted tumor suppressor genes is rarely observed in vivo following treatment with DNA methylation inhibitors. A recent study revealed an unexpected requirement for CpG methylation in the synthesis and assembly of the ribosome, an essential function for cell growth and proliferation. As such, the data provide an unforeseen explanation of the action of DNA methylation inhibitors in restricting cancer cell growth.

摘要

人类基因组中 CpG 甲基化印迹模式的“突变”与许多疾病有关,包括癌症。特别是,在许多癌症中观察到肿瘤抑制基因的 CpG 甲基化获得导致的异常印迹,因此代表了基因“突变”和肿瘤进展的重要替代途径。DNA 甲基化抑制剂在治疗某些癌症方面具有治疗效果,人们假设这些效果是由于“突变”基因印迹的逆转。然而,在用 DNA 甲基化抑制剂治疗后,在体内很少观察到印迹的肿瘤抑制基因的显著重新激活。最近的一项研究揭示了 CpG 甲基化在核糖体的合成和组装中的意外需求,这是细胞生长和增殖的基本功能。因此,这些数据提供了对 DNA 甲基化抑制剂在限制癌细胞生长方面的作用的意外解释。

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