Altered microRNA expression patterns in irradiated hematopoietic tissues suggest a sex-specific protective mechanism
Altered microRNA expression patterns in irradiated hematopoietic tissues suggest a sex-specific protective mechanism
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DOI：
10.1016/j.bbrc.2008.09.080
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发表时间：
2008-12-05
影响因子：
3.1
通讯作者：
Kovalchuk, Olga
中科院分区：
文献类型：
--
作者：
Ilnytskyy, Yaroslav;Zemp, Franz J.;Kovalchuk, Olga
为了研究miRNAs在辐射反应中的参与，我们使用microRNAome分析来分析辐射敏感的造血淋巴组织的性别特异性反应。我们发现，辐射暴露导致小鼠脾脏和胸腺组织中microRNA表达的显着和性别特异性失调。在受调控的miRNAs中，我们发现miR-34 a和miR-7的表达变化可能参与了抵抗辐射细胞毒性的重要保护机制。我们观察到肿瘤抑制因子miR-34 a的表达显著增加，而其靶癌基因NOTCH 1、MYC、E2 F3和细胞周期蛋白D1的表达减少。此外，我们发现miR-7靶向淋巴特异性解旋酶LSH，这是DNA甲基化和基因组稳定性的关键调节因子。而miR-7显著下调，LSH显著上调。这些细胞变化可能构成对抗辐射诱导的低甲基化的所有尝试。组织特异性的miRNA反应和可能的调控照射后的miRNA表达进行了讨论。(C)2008年爱思唯尔公司All rights reserved.
To investigate involvement of miRNAs in radiation responses We used microRNAome profiling to analyze the sex-specific response of radiation sensitive hematopoietic lymphoid tissues. We show that radiation exposure resulted in a significant and sex-specific deregulation of microRNA expression in murine spleen and thymus tissues. Among the regulated miRNAs, we found that changes in expression of miR-34a and miR-7 may be involved in important protective mechanisms counteracting radiation cytotoxicity. We observed a significant increase in the expression of tumor-suppressor miR-34a, paralleled by a decrease in the expression of its target oncogenes NOTCH 1, MYC, E2F3 and cyclin D1. Additionally, we show that miR-7 targets the lymphoid-specific helicase LSH, a pivotal regulator of DNA methylation and genome stability. While miR-7 was significantly down-regulated LSH was significantly up-regulated. These cellular changes may constitute all attempt to Counteract radiation-induced hypomethylation. Tissue specificity of miRNA responses and possible regulation of miRNA expression upon irradiation are discussed. (C) 2008 Elsevier Inc. All rights reserved.