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微小 RNA 与 DNA 损伤反应:对癌症治疗的启示。

MicroRNAs and DNA damage response: implications for cancer therapy.

机构信息

Howard Hughes Medical Institute, Human Biology and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

出版信息

Cell Cycle. 2013 Jan 1;12(1):32-42. doi: 10.4161/cc.23051. Epub 2012 Dec 19.

Abstract

The DNA damage response (DDR) pathways play critical roles in protecting the genome from DNA damage. Abrogation of DDR often results in elevated genomic instability and cellular sensitivity to DNA damaging agents. Many proteins involved in DDR are subjected to precise regulation at multiple levels, such as transcriptional control and posttranslational modifications, in response to DNA damage. MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. The expression levels of some miRNAs change in response to DNA damage. Some miRNAs, such as miR-24, 138, 96 and 182, have been implicated in DDR and/or DNA repair and affect cellular sensitivity to DNA damaging agents. In this review, we summarize recent findings related to the emerging roles of miRNAs in regulating DDR and DNA repair and discuss their potential in cancer therapy.

摘要

DNA 损伤应答 (DDR) 途径在保护基因组免受 DNA 损伤方面发挥着关键作用。DDR 的缺失通常会导致基因组不稳定性增加和细胞对 DNA 损伤剂的敏感性增加。许多参与 DDR 的蛋白质在多个水平上受到精确的调节,例如转录控制和翻译后修饰,以响应 DNA 损伤。microRNAs (miRNAs) 是一类小的非编码 RNA,在转录后水平负调控基因表达。一些 miRNAs 的表达水平会响应 DNA 损伤而发生变化。一些 miRNAs,如 miR-24、138、96 和 182,已被牵连到 DDR 和/或 DNA 修复中,并影响细胞对 DNA 损伤剂的敏感性。在这篇综述中,我们总结了 miRNA 调节 DDR 和 DNA 修复的新兴作用的最新发现,并讨论了它们在癌症治疗中的潜在应用。

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