Ilnytskyy Yaroslav, Zemp Franz J, Koturbash Igor, Kovalchuk Olga
Department of Biological Sciences, University of Lethbridge, Lethbridge, Alta, Canada.
Biochem Biophys Res Commun. 2008 Dec 5;377(1):41-5. doi: 10.1016/j.bbrc.2008.09.080. Epub 2008 Sep 26.
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 NOTCH1, 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 an attempt to counteract radiation-induced hypomethylation. Tissue specificity of miRNA responses and possible regulation of miRNA expression upon irradiation are discussed.
为了研究微小RNA（miRNA）在辐射反应中的作用，我们使用微小RNA组分析来分析辐射敏感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miRNA表达出现显著的性别特异性失调。在受调控的miRNA中，我们发现miR-34a和miR-7表达的变化可能参与了对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-34a的表达显著增加，同时其靶标癌基因NOTCH1、MYC、E2F3和细胞周期蛋白D1的表达下降。此外，我们发现miR-7靶向淋巴特异性解旋酶LSH，LSH是DNA甲基化和基因组稳定性的关键调节因子。当miR-7显著下调时，LSH显著上调。这些细胞变化可能是为了对抗辐射诱导的低甲基化。本文还讨论了miRNA反应的组织特异性以及辐射后miRNA表达的可能调控。
