FOXM1-mediated regulation of reactive oxygen species and radioresistance in oral squamous cell carcinoma cells
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ABSTRACT:
PROVIDER: PRJNA868325 | ENA |
REPOSITORIES: ENA
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Project description:Radioresistance is a major obstacle to the successful treatment of oral squamous cell carcinoma (OSCC). To help overcome this issue, we have developed clinically relevant radioresistant (CRR) cell lines, generated by irradiating parental cells over time, which are useful for OSCC research. In the present study, we conducted gene expression analysis using CRR cells and their parental lines to investigate the regulation of radioresistance in OSCC cells. Based on gene expression changes over time in CRR cells and parental lines subjected to irradiation, forkhead box M1 (FOXM1) was selected for further analysis in terms of its expression OSCC cell lines, including CRR cell lines, and clinical specimens. We suppressed or upregulated the expression of FOXM1 in OSCC cell lines, including CRR cell lines, and examined radiosensitivity, DNA damage, and cell viability under various conditions. The molecular network regulating radiotolerance was also investigated, especially the redox pathway, and the radiosensitizing effect of FOXM1 inhibitors was examined as a potential therapeutic application. We found that FOXM1 was not expressed in normal human keratinocytes but was expressed in several OSCC cell types. The expression of FOXM1 was upregulated in CRR cells compared with that detected in the parental cell lines. In clinical specimens, FOXM1 expression was upregulated in cells that survived irradiation. FOXM1-specific siRNA treatment increased radiosensitivity, whereas FOXM1 overexpression decreased radiosensitivity, and DNA damage was altered significantly under both conditions as well as the levels of redox-related molecules and reactive oxygen species production. Treatment with the FOXM1 inhibitor thiostrepton had a radiosensitizing effect and overcame radiotolerance in CRR cells. According to these results, the FOXM1-mediated regulation of reactive oxygen species could be a novel therapeutic target for the treatment of radioresistant OSCC; thus, treatment strategies targeting this axis might overcome radioresistance in this disease.
2022-10-01 | GSE210922 | GEO
Project description:Radioresistance is a predominant obstacle of effective treatments in non-small cell lung cancer (NSCLC), while the underlying mechanism remains incompletely elucidated. Spindlin 1(SPIN1) has been reported to participate in tumor initiation and progression, while its role in NSCLC tumorigenesis and radioresistance remains largely unknown. In this study, bioinformatics analysis, immunohistochemistry (IHC) and western blotting assays were performed to test SPIN1 expression in NSCLC samples and cell lines. The carcinogenic role of SPIN1 was evaluated by cell growth and proliferation, EdU staining, transwell and colony formation assays. Besides, the radiosensitivity of NSCLC cells was determined by clonogenic cell survival, neutral comet and γ-H2AX and Rad51 foci formation assays. Xenograft tumor model was constructed to access the effects of SPIN1 on tumorigenesis and radiosensitivity. Furthermore, RNA sequencing, quantitative real-time PCR, CHX and ubiquitination assays were applied to elucidate the correlation between SPIN1 and FOXO3a-FOXM1 axis. Therefore, our results suggest that the SPIN1-MDM2-FOXO3a/FOXM1 signaling axis is essential for NSCLC progression and radioresistance, and it could serve as therapeutic targets in irradiation-resistance NSCLC.
2024-11-20 | GSE276500 | GEO
Project description:Oral squamous cell carcinoma (OSCC) is not significant improved in prognosis despite advancement in treatments. The presence of treatment resistant OSCC is responsible for stagnation in the survival rate. The inter-cellular communications between tumor cells is one of the molecular mechanisms involved in the acquisition of treatment resistance of OSCC. Extracellular vesicles (EVs) and encapsulated miRNAs are important mediators of the inter-cellular communication. We searched for miRNAs involved in radioresistance of OSCC, in order to elucidate the mechanism of acquisition of radioresistance
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Project description:Glioblastoma multiforme (GBM) is a persistent challenge in oncology due to its aggressive nature and limited survival. Despite various therapeutic strategies, the recurrence of GBM still exists, driven by the complex cellular diversity and evolutionary dynamics during the treatment process. This study established a radioresistant GBM cell model through repeated exposure to ionizing radiation and revealed a distinct manifestation of cellular senescence of these cells. The comprehensive genomic and transcriptomic analyses identified that IFI16, as a critical driver of cellular senescence, contributed to the radioresistance of GBM. Mechanistically, IFI16 was involved in orchestrating HMOX1 transcription thereby attenuating ferroptosis after irradiation. HMOX1 limited lipid peroxidation, reactive oxygen species (ROS) production, and intracellular Fe2+ content following irradiation, thus effectively counteracting ferroptosis in GBM. Furthermore, IFI16 interacted with the transcription factors JUND and SP1 through its pyrin domain, robustly facilitating HMOX1 expression, further inhibiting ferroptosis and enhancing radioresistance in GBM cells. Notably, glyburide, an anti-aging agent, effectively disrupted IFI16 function and thus enhanced ferroptosis and radiosensitivity. By specifically targeting the pyrin domain of IFI16, glyburide emerged as a potential therapeutic agent against GBM radioresistance. In conclusion, these novel findings underscored the central role of IFI16 in GBM radioresistance and offered promising avenues for innovative therapeutic interventions against GBM radiosensitivity
2024-12-25 | GSE274090 | GEO
Project description:To identify components involved in the signal transduction and activation of the singlet oxygen-mediated response, a mutant selection was performed. This led to the isolation of the singlet oxygen resistant 1 (sor1) mutant, which is more tolerant to singlet oxygen-producing chemicals and shows a constitutively higher expression of GPXH and GSTS1. Map-based cloning revealed that the SOR1 gene encodes a novel bZIP transcription factor, which seems to control its own expression as well as that of a large number of oxidative stress response and detoxification genes. In the promoter region of many of these genes a highly conserved 8-bp palindromic sequence element was found to be enriched. This element was shown to be essential for GSTS1 overexpression in sor1 and for induction by increased levels of lipophilic reactive electrophile species (RES) suggesting that it functions as an electrophile response element (ERE). RES can be formed after singlet oxygen-induced lipid peroxidation, indicating that a RES-stimulated and SOR1-mediated response of detoxification genes is part of the singlet oxygen-induced acclimation process in C. reinhardtii. The sor1 mutant isolated in a screen for singlet oxygen resistant mutants and the corresponding wild-type strain 4A+ were grown in a 12 h light dark cycle for several days before total RNA was extracted 6 h after the light came on.
2012-04-03 | E-GEOD-33548 | biostudies-arrayexpress
Project description:To identify components involved in the signal transduction and activation of the singlet oxygen-mediated response, a mutant selection was performed. This led to the isolation of the singlet oxygen resistant 1 (sor1) mutant, which is more tolerant to singlet oxygen-producing chemicals and shows a constitutively higher expression of GPXH and GSTS1. Map-based cloning revealed that the SOR1 gene encodes a novel bZIP transcription factor, which seems to control its own expression as well as that of a large number of oxidative stress response and detoxification genes. In the promoter region of many of these genes a highly conserved 8-bp palindromic sequence element was found to be enriched. This element was shown to be essential for GSTS1 overexpression in sor1 and for induction by increased levels of lipophilic reactive electrophile species (RES) suggesting that it functions as an electrophile response element (ERE). RES can be formed after singlet oxygen-induced lipid peroxidation, indicating that a RES-stimulated and SOR1-mediated response of detoxification genes is part of the singlet oxygen-induced acclimation process in C. reinhardtii.
2012-04-03 | GSE33548 | GEO
Project description:Phytochrome B regulates reactive oxygen signaling during stress in plants.
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Project description:Renal Proximal Tubular Cells of young / senescent replicative age or high / low reactive oxygen species content were profiled using an Affymetrix Chip Platform.<br>Sample classifications: <br>Young refers to the in vitro age of early passage cells. <br>Senescent indicates cells at the end of their in vitro life span, having entered an irreversible growth arrest. <br>SortHI refers to cells with high intracellular reactive oxygen species content that were sorted by FACS according to a bright FL1 fluorescence after staining with 1 ï¾µM CM-H2DCFDA (Molecular Probes Cat No C6827).<br>SortLO refers to cells with low intracellular reactive oxygen species content that were sorted by FACS according to a dim FL1 fluorescence after staining with 1 ï¾µM CM-H2DCFDA.<br>
2011-01-15 | E-MEXP-2683 | biostudies-arrayexpress
Project description:mitochondrial electron transport in Arabidopsis leaves was blocked by antimycin A treatment to trigger mitochondrial production of reactive oxygen species and to study transcriptional changes in response
2010-12-31 | E-TABM-641 | biostudies-arrayexpress
Project description:Metabolic determinants of cellular fitness dependent on mitochondrial reactive oxygen species
| PRJNA663327 | ENA