Radiation-induced gene translation profiles reveal tumor type and cancer specific components
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE10547 | GEO | 2008/04/15
SECONDARY ACCESSION(S): PRJNA107911
REPOSITORIES: GEO
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Project description:The goal of this study was to compare the radiation-induced gene translation profiles generated from human tumor cell lines that are treated with radiation. Keywords: stimulus or stress design A panel of cell lines included 5 gliomas, 4 pancreatic carcinomas, 3 breast carcinomas and 2 non-small cell lung carcinomas. In addition, radiation-induced gene translation profiles were generated for 4 normal human cell lines: a skin fibroblast (BJ), 2 lung fibroblasts (MRC5, MRC9) and mammary epithelial (MEC). Specifically, cell lines were exposed to 2 Gy or sham irradiated, polysome-bound RNA was isolated 6h later and subjected to microarray analyses. Each cell line was evaluated in biological replicates.
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Project description:Deinococcus deserti is a desiccation- and radiation-tolerant desert bacterium. Differential RNA sequencing was performed to explore the specificities of its transcriptome. Strikingly, for 1174 (60%) mRNAs the transcription start site was found exactly at (916 cases, 47%) or very close to the translation initiation codon AUG or GUG. Such proportion of leaderless mRNAs, which may resemble ancestral mRNAs, is unprecedented for a bacterial species. Proteomics showed that leaderless mRNAs are efficiently translated in D. deserti. Interestingly, we also found 173 additional transcripts with a 5’-AUG or 5’-GUG that would make them competent for ribosome binding and translation into novel small polypeptides. Fourteen of these are predicted to be leader peptides involved in transcription attenuation. Another 30 correlated with new gene predictions and/or showed conservation with annotated and non-annotated genes in other Deinococcus species, and five of these novel polypeptides were indeed detected by mass spectrometry. The data also allowed re-annotation of the start codon position of 257 genes, including several DNA repair genes. Moreover, several novel highly radiation-induced genes were found and their potential roles are discussed. Based on our RNA sequencing and proteogenomics data, we propose that translation of many of the novel leaderless transcripts, which may have resulted from single nucleotide changes and maintained by selective pressure, provides a new explanation for the generation of a cellular pool of small peptides important for protection of proteins against oxidation and thus for radiation/desiccation tolerance and adaptation to harsh environmental conditions.
2014-04-08 | GSE56058 | GEO
Project description:Cellular senescence constitutes a generally irreversible proliferation barrier, accompanied by macromolecular damage and metabolic rewiring. Several senescence types have been identified based on the initiating stimulus, such as replicative (RS), stress-induced (SIS) and oncogene-induced senescence (OIS). Reduced protein synthesis is considered a senescence hallmark, but whether this trait pertains to various senescence subtypes and if distinct molecular mechanisms are involved remain largely unknown. Here, we analyze large published or experimentally produced RNA-seq and Ribo-seq datasets to determine whether major translation-regulating entities such as ribosome stalling, the presence of uORFs/dORFs and IRES elements may differentially contribute to translation deficiency in senescence subsets. We show that translation-regulating mechanisms may not be directly relevant to RS, however uORFs are significantly enriched in SIS. Interestingly, ribosome stalling, uORF/dORF patterns and IRES elements comprise predominant mechanisms upon OIS, strongly correlating with Notch pathway activation. Our study provides for the first time evidence that major translation dysregulation mechanisms/patterns occur during cellular senescence, but at different rates depending on the stimulus type. The degree at which those mechanisms accumulate directly correlates with translation deficiency levels. Our thorough analysis contributes to elucidating crucial and so far unknown differences in the translation machinery and ribosome biogenesis between senescence subsets.
2023-08-31 | GSE225095 | GEO
Project description:Tumor cell radioresistance is a major challenge in radiotherapy. By contrast, radiation response heterogeneity of tumor cells is poorly understood. Here, we performed scRNA-seq and scATAC-seq of 6 Gy γ-ray treated human lung adenocarcinoma cells to dissect cellular radiation response heterogeneity from perspective of transcriptional and regulatory cell states. Notably, we observed heterogeneous radioresponsiveness in purified lung adenocarcinoma cells by qualified cellular radiation response based on transcriptional landscape. There was DNA repair and apoptosis related transcriptional cell state appeared post-irradiation. We identified gene markers in this radiation-associated cell state and screened promising targets for LUAD radiosensitization based on 107 transcriptomic data of radiotherapy treated LUAD patients from TCGA database. Besides, transcriptional cell states transition was obvious accompanied with radiation-induced cell cycle arrest in which cell-cell communication was a potential regulatory mechanism. Finally, we identified radiation-associated regulatory cell state and analyzed the regulatory network of key transcriptional factors in cellular radiation response.
2022-08-22 | GSE211617 | GEO
Project description:Nanostring gene expression analysis using tumors from mice treated with GLA, X-ray radiation or the combination of GLA and radiation showed that the combination of GLA and radiation has synergistic effect in modulating the tumor micronenvironment.
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Project description:Analysis of whole transcriptome gene expression in 6 groups of liver samples in mice: HCC induced by high-LET radiation, HCC induced by low-LET radiation, spontaneous HCC, non-tumor liver irradiated with high-LET radiation, non-tumor liver irradiated with low-LET radiation, normal liver without radiation.
2021-07-14 | GSE166653 | GEO
Project description:Protein concentrations evolve under greater evolutionary constraint than mRNA levels. In addition, translation efficiency of mRNA populations represents the chief determinant of basal protein concentrations. This raises a fundamental question as to how mRNA and protein levels are actively coordinated in dynamic systems responding to acute physiological stimuli. This report examines the contributions of mRNA abundance and translation efficiency to protein output in cells responding to oxygen stimulus. We show that alternative translation efficiencies, not mRNA levels, represent the major adaptive mechanism that governs the cellular response to perturbations in [O2]. This phenomenon is coordinated by eIF4F under atmospheric [O2] and the previously uncharacterized hypoxic eIF4F (eIF4FH) under low [O2]. The oxygen-regulated remodeling of translation efficiency enables oxygenated and hypoxic cells to produce surprisingly divergent translatomes of similar complexity, with minimal dependence on mRNA levels. Changes in mRNA concentrations observed between normoxic and hypoxic cells are likely neutral, as they are during evolution. We propose that mRNAs contain hard-wired translation efficiency determinants for their triage by the translation apparatus on [O2] stimulus.
2016-07-20 | MSV000079962 | MassIVE
Project description:Although ionizing radiation has been shown to influence gene transcription, little is known about the effects of radiation on gene translational efficiency. To obtain a genome-wide perspective of the effects of radiation on gene translation, microarray analysis was done on polysome-bound RNA isolated from irradiated human brain tumor cells; to allow for a comparison with the effects of radiation on transcription, microarray analysis was also done using total RNA. The number of genes whose translational activity was modified by radiation was f10-fold greater than those whose transcription was affected. The radiation-induced change in a gene’s translational activity was shown to involve the recruitment of existing mRNAs to and away from polysomes. Moreover, the change in a gene’s translational activity after irradiation correlated with changes in the level of its corresponding protein. These data suggest that radiation modifies gene expression primarily at the level of translation. In contrast to transcriptional changes, there was considerable overlap in the genes affected at the translational level among brain tumor cell lines and normal astrocytes. Thus, the radiation-induced translational control of a subset of mRNAs seems to be a fundamental component of cellular radioresponse. (Cancer Res 2006; 66(2): 1052-61)
2008-05-21 | GSE11517 | GEO