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Fractionated irradiation of breast cancer cells rewires a gene regulatory circuit towards a treatment-resistant stemness phenotype

ABSTRACT: Fractionated irradiation of breast cancer cells rewires a gene regulatory circuit towards a treatment-resistant stemness phenotype

PROVIDER: PRJNA783278 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17028149_1.fastq.gz	Fastqsanger.gz
	SRR17028149_2.fastq.gz	Fastqsanger.gz
	SRR17028150_1.fastq.gz	Fastqsanger.gz
	SRR17028150_2.fastq.gz	Fastqsanger.gz
	SRR17028151_1.fastq.gz	Fastqsanger.gz

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Fractionated irradiation of breast cancer cells rewires a gene regulatory circuit towards a treatment-resistant stemness phenotype

Project description:Radiotherapy is a potent component of the standard of care for breast cancer. However, surviving radioresistant cells can repopulate following treatment and provoke relapse. Better understanding of the molecular mechanisms of radiation resistance may help improve treatment of radioresistant tumours. To emulate radiation therapy at the cellular level, we exposed MCF7 breast cancer cells to daily radiation doses of 2 Gy up to an accumulated dose of 20 Gy. Fractionally irradiated cells (FIR20) displayed increased clonogenic survival and population doubling time as compared to age-matched sham-irradiated cells and untreated, parental MCF7 cells. RNA-sequencing revealed a core signature of 229 mRNAs and 7 circRNAs significantly altered in the FIR20 cells. The FIR20 cell transcriptome overlapped significantly with canonical radiation signatures, and demonstrated a remarkable commonality with radiation and endocrine therapy resistance expression profiles, suggesting crosstalk between both acquired resistance pathways. Using predictive analyses and functional enrichment, we identified a gene-regulatory network of circRNA and mRNA that promotes stemness and inflammatory signaling in FIR20 cells. We propose that these phenotypic traits render breast cancer cells more radioresistant and may therefore serve as potential modules for combination therapies.

2022-10-12 | GSE189495 | GEO

Fractionated irradiation of MCF7 breast cancer cells rewires a gene regulatory circuit towards a treatment-resistant stemness phenotype.

Project description: Not available

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Evaluation of Transcriptomic Change in Late-Delayed Radiation following Fractionated Whole Brain Irradiation and High Dose Total Body Irradiation in Non-Human Primates

Project description:Fractionated whole-brain irradiation for the treatment of intracranial neoplasia causes progressive neurodegeneration and neuroinflammation. The long-term consequences of high single dose brain irradiation are unknown. In order to assess the late effects of brain irradiation we have compared transcriptomic gene expression profiles from nonhuman primates (rhesus macaques, Macaca mulatta) receiving single dose total body irradiation to those given fractionated whole brain radiotherapy and control comparators. Gene expression profiles from the dorsolateral prefrontal cortex (Brodmann area 46), hippocampus, and deep white matter (centrum semiovale) were compared. The goals of this study were to identify novel potential molecular effects of radiation-induced brain injury, to evaluate regional differences in the cerebral radiation response, and to assess whether animals receiving high dose total body irradiation demonstrated similar transcriptomic patterns as those observed in animals receiving fractionated whole brain irradiation.

2019-03-27 | GSE120901 | GEO

Expression profiling of murine lung 70 days following exposure to fractionated or acute dose of 1.0 Gy 56Fe- particle irradiation

Project description:Irradiation of the K-rasLA1 mouse model with a fractionated dose of 1.0Gy 56Fe- particles increases the incidence of invasive carcinoma compared to unirradiated controls or those irradiated with an acute dose. Microarray profiling was perfromed on whole lungs from K-rasLA1 mice in order to determine global expression changes in the lung following radiation exposure. RNA was extracted from K-rasLA1 lungs from unirradiated control animals or those irradiated with a fractionated or acute dose of 1.0Gy 56Fe- particles 70 days post-irradiation when lungs are still histologically indistiguishable and only contain benign lesions.

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Expression profiling of murine lung 70 days following exposure to fractionated or acute dose of 1.0 Gy 56Fe- particle irradiation

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2019PREs_Particle-fractionated

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Gene expression profile of mouse Lewis lung carcinoma cell line treated with single or fractionated ionizing radiation doses

Project description:Radiotherapy is one of the most common therapies for cancer. Approximately half of all cancer patients will receive radiotherapy at some point during treatment. Consequences of IR treatment are dose dependent and different sensitivity to IR of various types of cells is well established. To reduce the damage of IR to most sensitive cells of normal (noncancerous) tissue radiotherapy is administered as fractionated dose treatment applying radiation in ~2 Gy fractions every 24 hours, 5 times per week. However, during the therapy intrinsic and acquired tumor radioresistance may result in treatment failures. Comprehensive mechanisms of the resistance to irradiation as well as mechanisms of cellular response to fractionated dose IR remain unclear. Therefore, in the present study we evaluated global gene expression changes in murine Lewis lung carcinoma LLC1 cells following X-ray irradiation of single 2 Gy or 10 Gy and 2 Gy x 5 fractionated doses.

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Fractionated Proton Irradiation does not Impair Hippocampal Dependent Short Term or Spatial Memory in Female Mice

Project description:The environment outside the Earth’s protective magnetosphere is a much more threatening and complex space environment. The dominant causes for radiation exposure, solar particle events and galactic cosmic rays, contain high-energy protons. In space, astronauts need healthy and highly functioning cognitive abilities, of which the hippocampus plays a key role. Therefore, understanding the effects of 1H exposure on hippocampal-dependent cognition is vital for de-veloping mitigative strategies and protective countermeasures for future missions. To investi-gate these effects, we subjected 6-month-old female CD1 mice to 0.75 Gy fractionated 1H (250 MeV) whole-body irradiation at the NASA Space Radiation Laboratory. The cognitive perfor-mance of the mice was tested 3 months after irradiation using Y-maze and morris water maze tests. Both sham-irradiated and 1H-irradiated mice significantly preferred exploration of the novel arm compared to the familiar and start arms, indicating intact spatial and short-term memory. Both groups statistically spent more time in the target quadrant, indicating spatial memory retention. There were no significant differences in neurogenic and gliogenic cell counts after irradiation. In addition, proteomic analysis revealed no significant upregulation or down-regulation of proteins related to behavior, neurological disease, or neural morphology. Our data suggests 1H exposure does not impair hippocampal-dependent spatial or short-term memory in female mice.

2022-10-14 | PXD035933 | Pride

Evaluation of Transcriptomic Change in Late-Delayed Radiation following Fractionated Whole Brain Irradiation and High Dose Total Body Irradiation in Non-Human Primates

Project description:Evaluation of Transcriptomic Change in Late-Delayed Radiation following Fractionated Whole Brain Irradiation and High Dose Total Body Irradiation in Non-Human Primates

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