Department of Radiation Oncology, Tianjin Huan Hu Hospital, Tianjin 300060, China.
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, United States.
Mutat Res Rev Mutat Res. 2015 Jan-Mar;763:202-11. doi: 10.1016/j.mrrev.2014.11.003. Epub 2014 Nov 13.
Non-coding RNAs play a crucial role in maintaining genomic stability which is essential for cell survival and preventing tumorigenesis. Through an extensive crosstalk between non-coding RNAs and the canonical DNA damage response (DDR) signaling pathway, DDR-induced expression of non-coding RNAs can provide a regulatory mechanism to accurately control the expression of DNA damage responsive genes in a spatio-temporal manner. Mechanistically, DNA damage alters expression of a variety of non-coding RNAs at multiple levels including transcriptional regulation, post-transcriptional regulation, and RNA degradation. In parallel, non-coding RNAs can directly regulate cellular processes involved in DDR by altering expression of their targeting genes, with a particular emphasis on miRNAs and lncRNAs. MiRNAs are required for almost every aspect of cellular responses to DNA damage, including sensing DNA damage, transducing damage signals, repairing damaged DNA, activating cell cycle checkpoints, and inducing apoptosis. As for lncRNAs, they control transcription of DDR relevant gene by four different regulatory models, including signal, decoy, guide, and scaffold. In addition, we also highlight potential clinical applications of non-coding RNAs as biomarkers and therapeutic targets for anti-cancer treatments using DNA-damaging agents including radiation and chemotherapy. Although tremendous advances have been made to elucidate the role of non-coding RANs in genome maintenance, many key questions remain to be answered including mechanistically how non-coding RNA pathway and DNA damage response pathway is coordinated in response to genotoxic stress.
非编码 RNA 在维持基因组稳定性方面发挥着关键作用，而基因组稳定性对于细胞存活和预防肿瘤发生至关重要。通过非编码 RNA 与经典 DNA 损伤反应 (DDR) 信号通路之间的广泛交流，DDR 诱导的非编码 RNA 的表达可以提供一种调节机制，以时空方式准确控制 DNA 损伤反应基因的表达。从机制上讲，DNA 损伤会在多个层面改变多种非编码 RNA 的表达，包括转录调控、转录后调控和 RNA 降解。同时，非编码 RNA 可以通过改变其靶向基因的表达，直接调节 DDR 涉及的细胞过程，特别是 miRNA 和 lncRNA。miRNA 几乎参与细胞对 DNA 损伤的各个方面的反应，包括感知 DNA 损伤、转导损伤信号、修复受损 DNA、激活细胞周期检查点和诱导细胞凋亡。至于 lncRNA，它们通过四种不同的调控模式控制 DDR 相关基因的转录，包括信号、诱饵、向导和支架。此外，我们还强调了非编码 RNA 作为使用包括辐射和化疗在内的 DNA 损伤剂的抗癌治疗的生物标志物和治疗靶点的潜在临床应用。尽管已经取得了巨大的进展来阐明非编码 RNA 在基因组维护中的作用，但仍有许多关键问题需要回答，包括在遗传毒性应激下，非编码 RNA 途径和 DNA 损伤反应途径如何协调的机制问题。
