title: Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells.
abstract: Long non-coding RNAs (lncRNAs) are non-protein coding transcripts that modulate mRNA and microRNA (miRNA) expression, thereby controlling multiple cellular processes, including transcriptional regulation of gene expression, cell differentiation and apoptosis. Ionizing radiation (IR), a strong cellular stressor, is known to influence gene expression of irradiated cells, mainly by activation of oxidative processes. Whether and how IR also affects lncRNA expression in human peripheral blood mononuclear cells (PBMCs) is still poorly understood. Exposure of PBMCs to IR dose-dependently activated p53 and its downstream target p21, ultimately leading to cell-cycle arrest and/or apoptosis. Cleavage of caspase-3, a specific process during apoptotic cell death, was detectable at doses as low as 30 Gy. Transcriptome analysis of 60 Gy-irradiated PBMCs revealed a strong time-dependent regulation of a variety of lncRNAs. Among many unknown lncRNAs we also identified a significant upregulation of Trp53cor1, MEG3 and TUG1, which have been shown to be involved in the regulation of cell cycle and apoptotic processes mediated by p53. In addition, we found 177 miRNAs regulated in the same samples, including several miRNAs that are known targets of upregulated lncRNAs. Our data show that IR dose-dependently regulates the expression of a wide spectrum of lncRNAs in PBMCs, suggesting a crucial role for lncRNAs in the complex regulatory machinery activated in response to IR.
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Austria.
authors.forename: Lucian
authors.initials: L
authors.lastname: Beer
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.|Molecular Biotechnology, University of Applied Sciences FH Campus Wien, Vienna, Austria.
authors.forename: Lucas
authors.initials: L
authors.lastname: Nemec
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.
authors.forename: Tanja
authors.initials: T
authors.lastname: Wagner
authors.affiliation: Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Vienna, Austria.
authors.forename: Robin
authors.initials: R
authors.lastname: Ristl
authors.affiliation: Department of Dermatology, Research Division of Biology and Pathobiology of the Skin, Medical University of Vienna, Vienna, Austria.
authors.forename: Lukas M
authors.initials: LM
authors.lastname: Altenburger
authors.affiliation: Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Austria.|Department of Thoracic Surgery, Medical University of Vienna, Austria.|Head FFG Project 852748 'APOSEC', FOLAB Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
authors.affiliation: Department of Dermatology, Research Division of Biology and Pathobiology of the Skin, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000528:radiation effects*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D025341:Principal Component Analysis; D062085:RNA, Long Noncoding / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53
keywords: PBMC; apoptosis; lncRNA; p53; paracrine; radiation