Dataset Information

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.

SUBMITTER: Beer L

PROVIDER: S-EPMC5603904 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells.

Beer Lucian L Nemec Lucas L Wagner Tanja T Ristl Robin R Altenburger Lukas M LM Ankersmit Hendrik Jan HJ Mildner Michael M

Journal of radiation research 20170301 2

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 mononuc ...[more]

PMID: 27974506

Similar Datasets

Project description: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.

Project description:Background:Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression in the immune system, but their impact on neuropsychiatric systemic lupus erythematosus (NPSLE) remains unknown. Methods:RNA sequencing analysis was used to screen the comprehensive expression profile of lncRNAs and messenger RNAs (mRNAs) in peripheral blood mononuclear cells (PBMCs) from NPSLE patients, active SLE patients who had never experienced neuropsychiatric manifestations (Non-NPSLE) and healthy controls. Differentially expressed (DE) lncRNA levels were validated by qRT-PCR in 26 NPSLE patients, 31 Non-NPSLE patients and 30 healthy controls. Further, correlations of DE lncRNAs with clinical manifestations of NPSLE patients were analyzed. Finally, a bioinformatic analysis was performed to investigate the potential functions of DE genes. Results:Four hundred and fifty-one lncRNAs and 272 mRNAs were DE between the NPSLE patients and Non-NPSLE patients, among which, significantly upregulated expression levels of NONHSAT208182.1, NONHSAT182114.1, NONHSAT106801.2, NONHSAT039491.2, ENST00000356215, NONHSAT087499.2 and NONHSAT207026.1 while downregulated expression levels of NONHSAT001281.2 and NONHSAT024353.2 were further validated in PBMCs from NPSLE patients by qRT-PCR. Bioinformatic analysis suggested several gene ontology (GO) terms and signal pathways may play important roles in NPSLE development. Co-expression networks analysis indicated that 170 lncRNAs and 46 mRNAs were included in the co-expression network. The expression level of NONHSAT039491.2 was associated with the activity of SLE and the presence of anti-dsDNA, anti-RNP antibody, dizziness and headache. NONHSAT087499.2 level correlated with anti-RNA antibody, ENST00000356215 level correlated with olfactory threshold and oral ulcer. NONHSAT208182.1 level correlated with the presence of fever, unstable walking and urinary red blood cells. NONHSAT106801.2 correlated with frequency of B cells and the presence of fever. NONHSAT024353.2 level was associated with serum IgG levels and the presence of anti-SSA and disorder of consciousness. Conclusions:Our data provided comprehensive evidence regarding the differential expression of lncRNAs in PBMCs from NPSLE patients, indicating that these DE lncRNAs may play roles in NPSLE development. Our finding shed light on the understanding of the molecular mechanisms of lncRNAs in the pathogenesis of NPSLE.

Dataset Information

Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells.

Publications

Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets