Sex-specific radiation-induced microRNAome responses in the hippocampus, cerebellum and frontal cortex in a mouse model
Sex-specific radiation-induced microRNAome responses in the hippocampus, cerebellum and frontal cortex in a mouse model
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DOI：
10.1016/j.mrgentox.2010.05.007
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发表时间：
2011-06-17
影响因子：
1.9
通讯作者：
Kovalchuk, Olga
中科院分区：
文献类型：
--
作者：
Koturbash, Igor;Zemp, Franz;Kovalchuk, Olga
电离辐射是一种重要的治疗方式，但它也是一种众所周知的基因毒性物质，能够破坏细胞和组织。因此，放射治疗会对暴露的组织和器官造成许多副作用。放射治疗是脑癌患者一线治疗方案的一部分，但可能导致暴露的脑组织发生严重的功能和形态变化。然而，大脑中辐射诱导效应的机制尚不清楚，研究尚不充分。最近的数据表明，短rna，特别是microrna，在辐射反应中很重要，但对辐射诱导的大脑microRNAome的变化一无所知。我们分析了x射线照射对雄性和雌性小鼠海马、额叶皮层和小脑中microRNA表达的影响。在这里，我们报告了组织、时间和性别特异性的脑辐射反应，并展示了microrna与其靶标之间相互作用的证据。具体来说，我们表明miR-29家族表达的变化可能与从头甲基转移酶DNMT3a表达的改变和全球DNA甲基化水平的改变有关，至少部分相关。此外，这些性别特异性的表观遗传变化可能与男性中辐射诱发癌症的患病率有关。我们发现了几种可能作为脑辐射暴露生物标志物的microrna。综上所述，我们的研究可能为进一步分析雄性和雌性小鼠不同脑区的microRNA表达以及详细解剖辐射引起的脑反应提供重要的路线图。(C) 2010 Elsevier B.V.版权所有
Ionizing radiation is an important treatment modality, but it is also a well-known genotoxic agent capable of damaging cells and tissues. Therefore radiation treatment can cause numerous side effects in exposed tissues and organs. Radiotherapy is a part of the front-line treatment regime for brain cancer patients, but can cause severe functional and morphological changes in exposed brain tissues. However, the mechanisms of radiation-induced effects in the brain are not well understood and are under-investigated. Recent data has implicated short RNAs, especially microRNAs, as important in radiation responses, yet nothing is known about radiation-induced changes in the brain microRNAome.We analyzed the effects of x-ray irradiation on microRNA expression in the hippocampus, frontal cortex, and cerebellum of male and female mice. Here, we report tissue-, time-, and sex-specific brain radiation responses, as well as show evidence of an interplay between microRNAs and their targets. Specifically, we show that changes in the expression of the miR-29 family may be linked, at least in part, to altered expression of de novo methyltransferase DNMT3a and changed global DNA methylation levels. Further, these sex-specific epigenetic changes may be correlated to the prevalence of radiation-induced cancers in males.We identified several microRNAs that can potentially serve as biomarkers of brain radiation exposure. In summary, our study may provide an important roadmap for further analysis of microRNA expression in different brain regions of male and female mice and for detailed dissection of radiation-induced brain responses. (C) 2010 Elsevier B.V. All rights reserved.