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NFATC2 modulates radiation toxicity in dermal fibroblasts from patients with severe side-effects of radiotherapy

ABSTRACT: Although it is well established that 5 to 15% of radiotherapy patients exhibit severe side-effects in healthy tissue, the cellular and molecular mechanisms involved are still poorly known, and the link between cellular and tissue radiosensitivity is still debated. We here studied fibroblasts from normal skin of patients with severe sequels of radiotherapy in order to examine if specific basal cell activities might be involved in susceptibility to side-effects. When compared to control cells, patient fibroblasts exhibited higher radiosensitivity and defects in DNA double strand breaks (DSB) repair and 8-oxoGuanines, abasic sites and glycol damaged base repair. Transcriptome profiling of dermal fibroblast cell strains from 16 radiotherapy patients with severe side-effects and 8 healthy individuals identified 540 genes specifically deregulated in the patients. Nuclear factor of activated T cells 2 (NFATC2) was one of the most differentially expressed genes. This transcription factor involved in immune responses was found poorly expressed at transcript and protein level in patient cells, whereas the NFATC2 gene region was hypermethylated. Furthermore, NFATC2 expression correlated to the cell survival after irradiation. Finally, we observed that the silencing of NFATC2 in normal cells by RNA interference leads to increased cellular radiosensivity and defects in DNA DSB repair. This study demonstrates that patients with clinical hypersensitivity also exhibit intrinsic cellular radiosensitivity in normal skin cells. It further reveals a new role for NFATC2 as a potential regulator of the cellular sensitivity to ionizing radiations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE154559 | GEO | 2020/12/10

REPOSITORIES: GEO

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NFATC2 modulates radiation toxicity in dermal fibroblasts from patients with severe side-effects of radiotherapy

Project description:NFATC2 modulates radiation toxicity in dermal fibroblasts from patients with severe side-effects of radiotherapy

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