Sex-specific microRNAome deregulation in the shielded bystander spleen of cranially exposed mice
Sex-specific microRNAome deregulation in the shielded bystander spleen of cranially exposed mice
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DOI：
10.4161/cc.7.11.5981
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发表时间：
2008-06-01
期刊：
影响因子：
4.3
通讯作者：
Kovalchuk, Olga
中科院分区：
文献类型：
--
作者：
Koturbash, Igor;Zemp, Franz J.;Kovalchuk, Olga
旁观者效应是当暴露的细胞向它们幼稚的、未暴露的邻居发出痛苦信号时发生的一种现象。它现在被认为是辐射暴露的普遍后果。它在培养的细胞、3D组织模型以及器官和生物体中发生。尽管如此，旁观者效应的确切机制仍不清楚。最近的研究表明，旁观者效应可能在男性和女性中部分不同，并且可能通过短的非编码RNA，特别是microRNA介导。microRNA小，丰富，能够调节多种靶标的表达。然而，它们在旁观者效应中的作用还没有被详细分析。在体内旁观者效应中观察到的性别差异背后的机制也有待揭示。我们假设，辐射诱导的microRNA在暴露组织和旁观者组织中的表达在雄性和雌性中可能是不同的。使用一个成熟的旁观者小鼠模型，当动物的头部暴露时，而身体完全受到医用级防护罩的保护，我们第一次表明，辐射暴露触发了未暴露的旁观者脾脏中microRNAome的显著和性别特异性的失调。改变的miRNA水平被miRNA加工酶Dicer和RNA诱导沉默复合物（RISC）组分水平的性别特异性变化所掩盖。动物绝育导致microRNAome发生剧烈变化，并显著影响辐射和旁观者miRNA反应。我们的数据可能为进一步分析microRNAome在遗传毒性应激反应中的作用提供路线图，并可能帮助我们解释辐射诱导的致癌作用的性别特异性。
The bystander effect is a phenomenon that occurs when exposed cells signal distress to their naive, unexposed neighbors. It is now accepted as a ubiquitous consequence of radiation exposure. It is well documented to occur in cultured cells, 3D tissue models, and in organs and organisms. Notwithstanding, the exact mechanisms of the bystander effect remain unclear. Recent studies hinted that bystander effects may, in part, be distinct in males and females, and possibly mediated via short non-coding RNAs, specifically, microRNAs. MicroRNAs are small, abundant and capable of regulating the expression of a wide variety of targets. Yet, their roles in bystander effects have not been analyzed in detail. The mechanisms behind sex differences observed in in vivo bystander effects also remain to be uncovered.We hypothesized that the radiation-induced expression of microRNAs in exposed and bystander tissue may be distinct in males and females.Using a well-establish bystander mouse model when the animal's head is exposed, while the body is completely protected by a medical-grade shield, we have for the first time shown that radiation exposure triggers a significant and sex-specific deregulation of the microRNAome in the non-exposed bystander spleen. The altered miRNA levels were paralleled by sex-specific changes in the levels of the miRNA processing enzyme Dicer and components of the RNA-induced silencing complex (RISC). Sterilization of animals resulted in drastic microRNAome alterations and significantly affected radiation and bystander miRNA responses. Our data may provide a roadmap for further analysis of the role of microRNAome in genotoxic stress responses and may help us explain sex specificity of radiation-induced carcinogenesis.