Unraveling the global microRNAome responses to ionizing radiation in human embryonic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Mykyta Sokolov
PROVIDER: E-MEXP-3366 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The study aimed to elucidate the whole human genome wide changes in gene expression in cultured human embryonic stem cells after ionizing radiation exposures
2010-12-01 | E-MEXP-2596 | biostudies-arrayexpress
Project description:In this study, to delineate the radiation-induced changes in miRNAs and protein cargo, we established the microRNA and proteome profiles of plasma EVs collected from mice that had been sham- (SI), whole body (WBI), or partial body irradiated (PBI) with 2 Gy X-rays 24 hours before. The radiation-induced changes in the miRNA and protein composition of EVs can influence the stress response of distant cells by propagating damaging or protective signals. Testing EVs in functional assays may be a read out of the multiple radiation-induced signaling networks, crucial for gaining an understanding of the EVs properties. Therefore, to functionally elucidate the pathophysiological changes in the contents of EVs induced by irradiation, we here investigated the EV-induced cellular responses in vivo, by injecting WBI, PBI and SI plasma-derived EVs in the cerebellum of neonatal mice, highly susceptible to radiation injury, and evaluating the level of apoptosis.
2022-03-10 | PXD026408 | Pride
Project description:Inactivation of Pten occurs by multiple mechanisms including epigenetic silencing, point mutations, insertion, and deletion, which are tissue dependent. Although frequent loss of heterozygosity around Pten locus and plausible involvement of epigenetic silencing have been reported in radiation-induced thymic lymphomas, the frequency of Pten inactivation and the spectrum of causal aberrations have not yet been extensively characterized. Here, we assessed the principal mode of inactivation by comprehensively analyzing expression and alterations of Pten gene in 23 radiation-induced thymic lymphomas developed in B6C3F1 mice. We found no evidence for methylation-associated silencing of Pten gene. Instead, we found complex structural abnormalities in 8 lymphomas (35%) that included missense and nonsense mutations, 1- and 3-bp insertions, and focal deletions. Sequencing of deletion breakpoints suggested that illegitimate V(D)J recombination and microhomology-mediated rearrangement were responsible for the focal deletions. Seven out of these 8 lymphomas had biallelic alterations, and 4 of them did not express any Pten protein. These aberrations of Pten were well coincided with downstream Akt phosphorylation on Ser473. In conclusion, Pten inactivation, which is frequently biallelic and is caused by a variety of structural abnormalities but not by epigenetic silencing, is involved in radiation-induced lymphomagenesis. Three thymic lymphomas were analyzed by array-CGH method.
2010-05-06 | E-GEOD-17751 | biostudies-arrayexpress
Project description:Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age at exposure and their underlying mechanisms remain unclear. We analyzed the mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). T-cell lymphoma incidence did not show any statistical differences among three irradiated groups; however, the frequency of loss of heterozygosity on chromosomes 11 and 19 showed opposing correlations with age at exposure. Ikaros on chromosome 11 was mutated frequently in the young adultâ??irradiation group (63%; 5/8), frequently incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik11, which lacks two of the four zincâ??finger domains important for DNA binding). Pten on chromosome 19 was mutated more frequently in tumors from infant- (67%; 10/15) compared with young adult-irradiated mice (13%; 1/8, P = 0.041). Despite the presence of homozygous Pten mutations, DNA copy number was unchanged in the infant-irradiation group, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Taken together, our findings demonstrate that while deletions on chromosome 11 affecting the Ikaros locus are a prominent feature of young adult irradiation-induced T-cell lymphoma, tumors arising after infant irradiation suffer a second hit in the Pten gene by chromosome mis-segregation or recombination. This is the first report showing age-at-exposure associated radiation-induced genomic alterations in two key tumor suppressor genes linked to T-cell lymphomagenesis. These data are important for considering the risks associated with childhood exposure to radiation. 38 T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting at different ages (Infant: 1 week old (15 tumors), Adolescent: 4 weeks old (13 tumors), Young adult: 8 weeks old (10 tumors)) were analyzed.
2015-11-12 | E-GEOD-63349 | biostudies-arrayexpress
Project description:The aim of our study is to investigate and compare the effects of carbon and photon irradiation on microvascular endothelial cells. Therefore we irradiated human pulmonary microvascular endothelial cells (HPMEC) with either 2Gy Carbon or 6Gy Photon (bioequivalent doses) and performed microarray analysis both 2 hours (short-term effect) and 6 days (long-term effects) after irradiation. All experiments were performed in 3 biological replicates.
2023-11-02 | E-MEXP-3956 | biostudies-arrayexpress
Project description:Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 Gy or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation and cholesterol metabolism. We found significantly enhanced expression of pro-inflammatory cytokines (TNF-, TGF-, IL-1 and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low density lipoprotein (LDL) and oxidized LDL was increased whereas that of high density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.
2021-09-10 | PXD024446 | Pride
Project description:MicroRNA (miRNA) is a type of non-coding RNA that regulates the expression of its target genes by interacting with the complementary sequence of the target mRNA molecules. Recent evidence has shown that genotoxic stress induces miRNA expression, but the target genes involved and role in cellular responses remain unclear. We examined the role of miRNA in the cellular response to X-ray irradiation by studying the expression profiles of radio-responsive miRNAs and their target genes in cultured human cell lines. We found that expression of miR-574-3p was induced in the lung cancer cell line A549 by X-ray irradiation. Overexpression of miR-574-3p caused delayed growth in A549 cells. A predicted target site was detected in the 3'-untranslated region of the enhancer of the rudimentary homolog (ERH) gene, and transfected cells showed an interaction between the luciferase reporter containing the target sequences and miR-574-3p. Overexpression of miR-574-3p suppressed ERH protein production and delayed cell growth. This delay was confirmed by knockdown of ERH expression. Our study suggests that miR-574-3p may contribute to the regulation of the cell cycle in response to X-ray irradiation via suppression of ERH protein production. miRNA expression were measured at 1 and 3 h after exposure to doses of 0, 2 or 20 Gy. Microarray experiments were performed with duplicate for each experiment.
2014-03-14 | E-GEOD-30130 | biostudies-arrayexpress
Project description:The aim of our study is to investigate the effects of carbon ion and photon irradiation on A549 tumor cells and analyse how these effects are altered by PML knockdown. Therefore we created PML knockdown A549 cells (shPML) and irradiated them with either 2Gy carbon ion or 6Gy Photon (bioequivalent doses). 4 days after irradiation microarray analysis was performed. All experiments were performed in 3 biological replicates and control groups were transduced with an empty vector.
2023-11-02 | E-MEXP-3965 | biostudies-arrayexpress
Project description:Cytoplasmic RNA bound to eIF4E was pulled down from MDA-MB-231 cells to determine the influence of radiation on eIF4E mRNA binding 4 samples were analyzed with 3 biological replicates
2012-06-14 | E-GEOD-36179 | biostudies-arrayexpress
Project description:Polysome-bound mRNA was analyzed to determine the effects of INK128 and radiation on mRNA translation 4 samples were analyzed with 3 biological replicates
2014-02-03 | E-GEOD-48098 | biostudies-arrayexpress