1 Department of Heavy Ion Radiation Medicine, Institute of Modern Physics , Chinese Academy of Sciences, Lanzhou, China .
DNA Cell Biol. 2014 Oct;33(10):667-79. doi: 10.1089/dna.2014.2401. Epub 2014 Jun 6.
Increasing evidence demonstrates that the expression levels of microRNAs (miRNAs) significantly change upon ionizing radiation (IR) and play a critical role in cellular response to IR. Although several radiation responsive miRNAs and their targets have been identified, little is known about how miRNAs expression and biogenesis is regulated by IR-caused DNA damage response (DDR). Hence, in this review, we summarize miRNA expression and biogenesis in cellular response to IR and mainly elucidate the regulatory mechanisms of miRNA expression and biogenesis from different aspects including ataxia-telangiectasia mutated (ATM) kinase, p53/p63/p73 family and other potential factors. Furthermore, we focus on ΔNp73, which might be a potential regulator of miRNA expression and biogenesis in cellular response to IR. miRNAs could effectively activate the IR-induced DDR and modulate the radiation response and cellular radiosensitivity, which have an important potential clinical application. Therefore, thoroughly understanding the regulatory mechanisms of miRNAs expression and biogenesis in radiation response will provide new insights for clinical cancer radiotherapy.
越来越多的证据表明,微小 RNA(miRNA)的表达水平在电离辐射(IR)后显著变化,并在细胞对 IR 的反应中发挥关键作用。虽然已经确定了几种辐射反应性 miRNA 及其靶标,但对于 miRNA 的表达和生物发生如何受到 IR 引起的 DNA 损伤反应(DDR)的调节知之甚少。因此,在这篇综述中,我们总结了 miRNA 在细胞对 IR 的反应中的表达和生物发生,并主要从共济失调毛细血管扩张突变(ATM)激酶、p53/p63/p73 家族和其他潜在因素等不同方面阐明了 miRNA 表达和生物发生的调节机制。此外,我们还重点关注了 ΔNp73,它可能是细胞对 IR 反应中 miRNA 表达和生物发生的潜在调节剂。miRNA 可以有效地激活 IR 诱导的 DDR,并调节辐射反应和细胞放射敏感性,具有重要的潜在临床应用。因此,深入了解 miRNA 在辐射反应中的表达和生物发生的调节机制将为临床癌症放射治疗提供新的见解。