High dose ionizing radiation regulates micro RNA and gene expression changes in human peripheral blood mononuclear cells

BMC Genomics

Hendrik Jan Ankersmit⁶  Michael Mildner⁵  Walter Klepetko⁶  Mariann Gyöngyösi²  Christian Gabriel⁴  Matthias Zimmermann⁶  Andreas Mitterbauer⁶  Mohammad Mahdi Kasiri⁶  Adolf Ellinger⁷  Robin Ristl³  Rudolf Seemann¹  Lucian Beer⁶ 

[1] University Hospital of Craniomaxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria;Department of Cardiology, Medical University Vienna, Vienna, Austria;Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Vienna, Austria;Austrian Cluster for Tissue Regeneration, Linz, Austria;Department of Dermatology, Research Division of Biology and Pathobiology of the Skin, Medical University Vienna, Lazarettgasse 14, 1090 Vienna, Austria;Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria;Department of Cell Biology and Ultrastructure Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria

关键词: Ionizing radiation;    p53;    Mononuclear leukocytes;    Apoptosis;    Messenger RNA;    MicroRNAs;    Microarray;   

Others  :  1139517
DOI  :  10.1186/1471-2164-15-814

 received in 2014-05-05, accepted in 2014-09-22,  发布年份 2014

【 摘 要 】

Background

High dose ionizing radiation (IR) induces potent toxic cell effects mediated by either direct DNA damage or the production of reactive oxygen species (ROS). IR-induced modulations in multiple biological processes have been proposed to be partly regulated by radiosensitive microRNA (miRNA). In order to gain new insights into the role of miRNAs in the regulation of biological processes after IR, we have investigated changes in mRNA and miRNA expression after high dose IR.

Results

IR induced changes in the mRNA and miRNA profiles of human peripheral blood mononuclear cells (PBMCs). When comparing non-irradiated and irradiated samples, we detected a time-dependent increase in differentially expressed mRNAs and miRNAs, with the highest differences detectable 20 hours after exposure. Gene ontology analysis revealed that very early events (up to 4 hours) after irradiation were specifically associated with p53 signaling and apoptotic pathways, whereas a large number of diverse cellular processes were deregulated after 20 hours. Transcription factor analysis of all up-regulated genes confirmed the importance of p53 in the early post-irradiation phase. When analyzing miRNA expression, we found 177 miRNAs that were significantly regulated in the late post-irradiation phase. Integrating miRNA and target gene expression data, we found a significant negative correlation between miRNA-mRNA and identified hepatic leukemia factor (HLF) as a transcription factor down-regulated in the response to IR. These regulated miRNAs and the HLF target genes were involved in modulating radio-responsive pathways, such as apoptosis, the MAKP signaling pathway, endocytosis, and cytokine-cytokine interactions.

Conclusion

Using a large dataset of mRNA and miRNA expression profiles, we describe the interplay of mRNAs and miRNAs in the regulation of gene expression in response to IR at a posttranscriptional level and their involvement in the modulation of radiation-induced biological pathways.

【 授权许可】

   
2014 Beer et al.; licensee BioMed Central Ltd.

【 图 表 】

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