Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA262312 | ENA |
REPOSITORIES: ENA
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Project description:With the aim to elucidate the etiology of radioresistance, we explored the genetic alterations in non-radioresistant vs. resistant esophageal cancer cells acquired by long-term fractionated radiation. We found AKR1C3, an aldo-keto reductase expressed seldom in most human tissues, expressed higher in radioresistance-acquired cells. Suppression of AKR1C3 via RNAi or its chemical inhibitors restored the sensitivity of the acquired tumor cells and xenograft BALB/c nude mice to ionizing radiation (IR). Cellular monitoring of the oxidative stress in the AKR1C3-elevated cells indicated that IR-induced ROS accumulation and the concomitant DNA damage was significantly alleviated, and such protective consequence disappeared upon AKR1C3 knockdown. These findings uncover the potential involvement of AKR1C3 in removal of cellular ROS and explain, at least partially, the acquired radioresistance by AKR1C3 overexpression. A retrospective analysis of esophageal carcinomas also indicated a significant expression of AKR1C3 in radio-resistant but not radio-sensitive surgical samples. Our study may provide a potential biomarker for predicting prognosis of radiotherapy and even direct a targeted therapy for esophageal cancer and other tumors.
2014-01-01 | S-EPMC4242615 | BioStudies
Project description:Elevated expression of AKR1C3 leads esophageal cancer resistant to ionizing radiation via modulation of oxidative stress
| PRJNA262310 | ENA
Project description:Elevated expression of AKR1C3 leads esophageal cancer resistant to ionizing radiation via modulation of oxidative stress (TE13)
| PRJNA262311 | ENA
Project description:With the aim to elucidate the etiology of radioresistance, we explored the genetic alterations in non-radioresistant vs. resistant esophageal cancer cells acquired by long-term fractionated radiation. We found AKR1C3, an aldo-keto reductase expressed seldom in most human tissues, expressed higher in radioresistance-acquired cells. Suppression of AKR1C3 via RNAi or its chemical inhibitors restored the sensitivity of the acquired tumor cells and xenograft nude mice to ionizing radiation (IR). We also found the potential involvement of AKR1C3 in removal of cellular ROS and explain, at least partially, the acquired radioresistance by AKR1C3 overexpression. Genome-wide profiling of gene expression in KY170R v. KY170 and TE13R v. TE13 using Illumine Human-6 V3 microarray indicated that over 900 genes were found to be remarkably differentiated. Among them, AKR1C3, an aldo-keto reductase existing at a low level in most human tissues, attracted our attention due to its significant expression in both radioresistant cells.
2014-09-27 | E-GEOD-61816 | ArrayExpress
Project description:With the aim to elucidate the etiology of radioresistance, we explored the genetic alterations in non-radioresistant vs. resistant esophageal cancer cells acquired by long-term fractionated radiation. We found AKR1C3, an aldo-keto reductase expressed seldom in most human tissues, expressed higher in radioresistance-acquired cells. Suppression of AKR1C3 via RNAi or its chemical inhibitors restored the sensitivity of the acquired tumor cells and xenograft nude mice to ionizing radiation (IR). We also found the potential involvement of AKR1C3 in removal of cellular ROS and explain, at least partially, the acquired radioresistance by AKR1C3 overexpression. Genome-wide profiling of gene expression in KY170R v. KY170 and TE13R v. TE13 using Illumine Human-6 V3 microarray indicated that over 900 genes were found to be remarkably differentiated. Among them, AKR1C3, an aldo-keto reductase existing at a low level in most human tissues, attracted our attention due to its significant expression in both radioresistant cells.
2014-09-27 | E-GEOD-61620 | ArrayExpress
Project description:With the aim to elucidate the etiology of radioresistance, we explored the genetic alterations in non-radioresistant vs. resistant esophageal cancer cells acquired by long-term fractionated radiation. We found AKR1C3, an aldo-keto reductase expressed seldom in most human tissues, expressed higher in radioresistance-acquired cells. Suppression of AKR1C3 via RNAi or its chemical inhibitors restored the sensitivity of the acquired tumor cells and xenograft nude mice to ionizing radiation (IR). We also found the potential involvement of AKR1C3 in removal of cellular ROS and explain, at least partially, the acquired radioresistance by AKR1C3 overexpression. Genome-wide profiling of gene expression in KY170R v. KY170 and TE13R v. TE13 using Illumine Human-6 V3 microarray indicated that over 900 genes were found to be remarkably differentiated. Among them, AKR1C3, an aldo-keto reductase existing at a low level in most human tissues, attracted our attention due to its significant expression in both radioresistant cells.
2014-09-27 | E-GEOD-61772 | ArrayExpress
Project description:Radiation therapy is an important treatment modality for esophageal cancer. However, acquisition of radioresistance ultimately results in esophageal cancer relapse. CD59, a membrane-bound complement regulatory protein, can transduce signals via a Src kinase in the lipid raft, thus playing a complement-independent role. However, the effect of CD59 on the esophageal cancer response to ionizing radiation remains unclear. In this study, we found that the expression level of CD59 was positively correlated with the radioresistance of esophageal cancer cell lines and clinical specimens. High CD59 expression indicated poor overall survival (OS) and disease-free survival (DFS) in esophageal squamous cell carcinoma (ESCC) patients who received radiotherapy. Genetic alteration of CD59 expression modulated the radiosensitivity of esophageal cancer cells to ionizing radiation. CD59 deficiency exacerbated DNA damage, hindered cell proliferation, and induced G2/M cell cycle arrest and cellular senescence, leading to an impaired DNA damage repair ability. In addition, CD59 deficiency almost completely reduced the phosphorylation of Src at Y416 despite ionizing radiation. A Src inhibitor saracatinib sensitized esophageal cancer cells to irradiation. Therefore, CD59 may be a potential biomarker for predicting the radioresistance of ESCC to radiotherapy.
2018-01-01 | S-EPMC6117325 | BioStudies
Project description:Deinococcus radiodurans is among a small number of bacterial species that are extremely resistant to ionizing radiation, UV light, toxic chemicals, and desiccation. We measured proteome oxidation (i.e., protein carbonylation, PC) in D. radiodurans as well as in standard and evolved resistant strains of Escherichia coli exposed to ionizing radiation or UVC light and found a consistent correlation with cell killing. The unique quantitative relationship between incurred PC and cell death holds over the entire range of killing for all tested bacteria and for both lethal agents, meaning that both bacterial species are equally sensitive to PC. We show that the extraordinary robustness of D. radiodurans depends on efficient proteome protection (but not DNA protection) against constitutive and radiation-induced PC consisting of low molecular weight cytosolic compounds. Remarkably, experimental evolution of resistance to ionizing radiation in E. coli coevolves with protection against PC. The decline in biosynthetic efficacy of the cellular proteome, as measured by the loss of reproduction of undamaged bacteriophage lambda in irradiated standard and evolved ionizing radiation-resistant E. coli, correlates with radiation-induced oxidative damage to host cells and their sensitivity to ionizing radiation. This correlation suggests that cell death by radiation is caused primarily by oxidative damage with consequential loss of maintenance activities including DNA repair.
1000-01-01 | S-EPMC2922536 | BioStudies
Project description:Deinococcus radiodurans R1 is extremely resistant to both oxidative stress and ionizing radiation. A simple and general targeted mutagenesis method was developed to generate catalase (katA) and superoxide dismutase (sodA) mutants. Both mutants were shown to be more sensitive to ionizing radiation than the wild type.
1999-01-01 | S-EPMC93425 | BioStudies
Project description:Ionizing radiation-induced changes to the redox balance does not only represent a risk for the cellular homeostasis, but can also induce a drastic modulation in the overall signalling system of cells. In the current study, effects of chronic exposure to ionizing gamma radiation were assessed in the radioresistant nematode Caenorhabditis elegans in order to understand whether antioxidant defences (AODs) could ameliorate radical formation, or if increased ROS levels would cause oxidative damage. This analysis was accompanied by phenotypical as well as molecular investigations, via assessment of reproductive capacity and somatic growth and differential gene expression through RNA sequencing. The use of a fluorescent reporter strain (sod1::gfp) and two ratiometric biosensors (Hyper and Grx1-roGFP2) demonstrated increased ROS production (H2O2) and activation of AODs (SOD1 and GPx) in vivo. The data indicate that at dose-rates ?10 mGy/h defence mechanisms were able to prevent the manifestation of oxidative stress. In contrast, at dose-rates ?40 mGy/h the constant formation of radicals induced a redox shift, which lead to oxidative damage responses, including changes in mitochondrial metabolism and functions, protein degradation, lipid metabolism, collagen synthesis and modulation of transcription. Moreover, genotoxic effects were among the most over-represented functions affected by chronic gamma irradiation, as indicated by differential regulation of genes involved in DNA damage, DNA repair, cell-cycle checkpoints, chromosome segregation and chromatin remodelling. Ultimately, the exposure to gamma radiation caused reprotoxic effects, with >20% reduction in the number of offspring per adult hermaphrodite at dose-rates ?40 mGy/h, accompanied by the down-regulation of more than 300 genes related to reproductive system, meiotic functions and gamete development and fertilization.
2019-10-17 | E-MTAB-8284 | BioStudies