Project description:In this study we screened for changes of DNA methylation in response to X-irradiation in the lymphoblastoid cell line GM12878 and the primary lung fibroblast cell line IMR90. We employed methylated DNA-Immunoprecipitation in combination with genome wide and region specific DNA microarrays to identify preferences of radiation induced changes of methylation with respect to genomic and epigenomic characteristics.
Project description:In this study we screened for changes of DNA methylation in response to X-irradiation in the lymphoblastoid cell line GM12878 and the primary lung fibroblast cell line IMR90. We employed methylated DNA-Immunoprecipitation in combination with genome wide and region specific DNA microarrays to identify preferences of radiation induced changes of methylation with respect to genomic and epigenomic characteristics.
Project description:In this study we addressed the question whether changes of DNA hydroxymethylation after X-ray irradiation occur in a random fashion or if they show preferences for specific regions or features. We did not only focus on gene loci and promotor sights but also on gene body hydroxymethylation alterations and associated changes in gene expression. A more profound insight into hydroxymethylation characteristics triggered by radiation could provide clues to mechanisms and consequences of cellular response to irradiation including the immediate consequence of DNA strand breaks associated with active DNA demethylation as well as the long term risk of tumorigenesis or other associated diseases.
Project description:X-rays are a form of ionizing radiation that has sufficient energy to remove electrons from atoms, thereby creating potentially harmful ions. X-ray irradiation during organogenesis can have profound detrimental effects, depending on the developmental stage and irradiating energy. In this study, we examined the impact of X-ray irradiation on zebrafish development at 36 h post-fertilization and observed marked jaw malformation, which was alleviated by folic acid pretreatment. Mechanistic studies revealed that folic acid pretreatment suppressed irradiation-induced production of reactive oxygen species. Transcriptome analysis performed at 24 h and 48 h post-irradiation revealed dysregulated expression of apolipoprotein A-IV a (apoa4a), methionine adenosyltransferase 1A (mat1a), heat shock protein 90 alpha class A member 1 tandem duplicate 1 (hsp90aa1.1), FKBP prolyl isomerase 5 (fkbp5), plac8 onzin related protein 3 (ponzr3), and prostaglandin E synthase 3a (ptges3a), which was not observed in zebrafish treated with folic acid-treated before the irradiation. These findings suggest that folic acid alleviates X-ray irradiation-induced jaw malformation in zebrafish, at least in part, by reducing oxidative stress and ameliorating dysregulated gene expression.
Project description:Keloid radiotherapy is clinically effective but has an incomplete underlying molecular mechanism and limited accessibility; we used X-ray exposure to identify effector pathways replicating its antifibrotic benefits without further radiation. After collecting patient keloid samples, primary human keloid fibroblasts and normal skin fibroblasts, non-targeted metabolomics and RNA-seq were performed, identifying phytosphingosine (PHS) and KIF20A as key mediators of fibrosis and cell death in keloid radiotherapy. X-ray irradiation increased PHS release in keloid fibroblasts; exogenous PHS and X-ray irradiation independently induced cell death and reduced fibrosis, their combination exerted radiosensitization by boosting G2/M arrest and apoptosis while lowering fibrosis progression, and both PHS and irradiation reduced KIF20A whose loss induced cell cycle arrest and apoptosis. Our findings reveal that X-ray irradiation enhances keloid fibroblast PHS secretion that downregulates KIF20A to exert keloid therapeutic effects, and topical PHS or KIF20A-targeting agents are immediately translatable alternatives for radiotherapy-ineligible patients.
Project description:Purpose: The goal of this study was to compare the lncRNA and mRNA expression profile of human fibroblast WS1 cells between 0 Gy and 5 Gy X-ray irradiation. Methods: lncRNA and mRNA-sequencing of WS1 cells were generated using Illuminal Hiseq4000, RNA-seq reads were mapped to human genome hg19 by hisat2 software. Cuffdiff software was used to analysis the differentially expressed levels of LncRNA and mRNA FPKM. Results: We identified different expressed levels of 88780 lnRNA and 20311 mRNA transcripts in WS1 cells between 0 Gy and 5 Gy X-ay irradiation. Conclusion: Our study first revealed the detail of lncRNA and mRNA expression profiles of WS1 cells after 5Gy of X-Ray irradiation
Project description:We report the application of RIP-sequencing technology for high-throughput profiling of ELAVL1 protein on the effect of lncRNA an mRNA in WS1 cells after 5 Gy X-ray irradiation
Project description:Current study aimed to identify the 400 mGy X-ray irradiation-induced unique gene expression changes in the hippocampus of the 9-month-old 3xTg-AD mice.