Differences in DNA Repair Capacity, Cell Death and Transcriptional Response after Irradiation between a Radiosensitive and a Radioresistant Cell Line

Borràs-Fresneda, Mireia; Barquinero, Joan Francesc; Gomolka, Maria; Hornhardt, Sabine; Rößler, Ute; Armengol, Gemma; Barrios, Leonardo

doi:10.1038/srep27043

Cited by 41 publications

(38 citation statements)

References 71 publications

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“…To exclude the possibility that genes in our core signature were predictors of a general response to genotoxic stress, we interrogated published datasets that used mild forms of DNA damage ([31]; GEO:GSE80207). Only one gene in our signature ( PLK3 ) was reported differentially expressed in a radiosensitive lymphoblast line 4 hr after exposure to 2 Gy ionizing radiation (false discovery rate [FDR] ≤ 0.05), a dose that causes damage without pervasive permanent cell-cycle arrest.…”

Section: Resultsmentioning

confidence: 99%

Unmasking Transcriptional Heterogeneity in Senescent Cells

et al. 2017

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SUMMARY Cellular senescence is a state of irreversibly arrested proliferation, often induced by genotoxic stress [1]. Senescent cells participate in a variety of physiological and pathological conditions, including tumor suppression [2], embryonic development [3, 4], tissue repair [5–8], and organismal aging [9]. The senescence program is variably characterized by several non-exclusive markers, including constitutive DNA damage response (DDR) signaling, senescence-associated β-galactosidase (SA-βgal) activity, increased expression of the cyclin-dependent kinase (CDK) inhibitors p16INK4A (CDKN2A) and p21CIP1 (CDKN1A), increased secretion of many bio-active factors (the senescence-associated secretory phenotype, or SASP), and reduced expression of the nuclear lamina protein LaminB1 (LMNB1) [1]. Many senescence-associated markers result from altered transcription, but the senescent phenotype is variable, and methods for clearly identifying senescent cells are lacking [10]. Here, we characterize the heterogeneity of the senescence program using numerous whole-transcriptome datasets generated by us or publicly available. We identify transcriptome signatures associated with specific senescence-inducing stresses or senescent cell types and identify and validate genes that are commonly differentially regulated. We also show that the senescent phenotype is dynamic, changing at varying intervals after senescence induction. Identifying novel transcriptome signatures to detect any type of senescent cell or to discriminate among diverse senescence programs is an attractive strategy for determining the diverse biological roles of senescent cells and developing specific drug targets.

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Section: Resultsmentioning

confidence: 99%

Unmasking Transcriptional Heterogeneity in Senescent Cells

et al. 2017

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“…The survival of DNA-damaged cancer cells is determined by whether cancer cells can repair damage to DNA (44,45). The current study revealed that the viability of Capan-1 cells was decreased and not in Panc-1 cells, and the difference was associated with a decrease of RAD51 expression.…”

Section: Discussionmentioning

confidence: 52%

Section: Pb Irradiation Decreases Rad51 Expression In Capan-1 Cellsmentioning

confidence: 99%

“…The fate of DNA-damaged cancer cells by chemotherapy and radiotherapy is determined by whether DNA damage is repaired (44,45). Therefore, the activities of DNA repair enzymes have been demonstrated to be closely associated with cell death and cell cycle arrest (45). RAD51, a homologous recombination repair enzyme, serves an important role in the repair of radiation-induced DNA damage and has been implicated as a radiosensitivity determinant (46).…”

Section: Pb Irradiation Decreases Rad51 Expression In Capan-1 Cellsmentioning

confidence: 99%

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The association of changes in RAD51 and survivin expression levels with the proton beam sensitivity of Capan‑1 and Panc‑1 human pancreatic cancer cells

Lee

Nam

2018

Int J Oncol

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Fewer than 20% of patients diagnosed with pancreatic cancer can be treated with surgical resection. The effects of proton beam irradiation were evaluated on the cell viabilities in Panc-1 and Capan-1 pancreatic cancer cells. The cells were irradiated with proton beams at the center of Bragg peaks with a 6-cm width using a proton accelerator. Cell proliferation was assessed with the MTT assay, gene expression was analyzed with semi-quantitative or quantitative reverse transcription-polymerase chain reaction analyses and protein expression was evaluated by western blotting. The results demonstrated that Capan-1 cells had lower cell viability than Panc-1 cells at 72 h after proton beam irradiation. Furthermore, the cleaved poly (ADP-ribose) polymerase protein level was increased by irradiation in Capan-1 cells, but not in Panc-1 cells. Additionally, it was determined that histone H2AX phosphorylation in the two cell lines was increased by irradiation. Although a 16 Gy proton beam was only slightly up-regulated cyclin-dependent kinase inhibitor 1 (p21) protein expression in Capan-1 cells, p21 expression levels in Capan-1 and Panc-1 cells were significantly increased at 72 h after irradiation. Furthermore, it was observed that the expression of DNA repair protein RAD51 homolog 1 (RAD51), a homogenous repair enzyme, was decreased in what appeared to be a dose-dependent manner by irradiation in Capan-1 cells. Contrastingly, the transcription of survivin in Panc-1 was significantly enhanced. The results suggest that RAD51 and survivin are potent markers that determine the therapeutic efficacy of proton beam therapy in patients with pancreatic cancer.

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“…Several recent studies showed that ncRNAs can modulate programmed cell death after IR [147,148]. Apoptosis is an acclaimed indicator of cellular radiosensitivity and a prognostic factor of radiotherapy treatment outcome [149,150]. Apart from apoptosis, cell death after IR can also occur via necrosis and mitotic catastrophe.…”

Section: Ncrnas Regulating Ir-induced Apoptosismentioning

confidence: 99%

Non-Coding RNAs in Cancer Radiosensitivity: MicroRNAs and lncRNAs as Regulators of Radiation-Induced Signaling Pathways

Podralska

Ciesielska

Kluiver

et al. 2020

Cancers

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Radiotherapy is a cancer treatment that applies high doses of ionizing radiation to induce cell death, mainly by triggering DNA double-strand breaks. The outcome of radiotherapy greatly depends on radiosensitivity of cancer cells, which is determined by multiple proteins and cellular processes. In this review, we summarize current knowledge on the role of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in determining the response to radiation. Non-coding RNAs modulate ionizing radiation response by targeting key signaling pathways, including DNA damage repair, apoptosis, glycolysis, cell cycle arrest, and autophagy. Additionally, we indicate miRNAs and lncRNAs that upon overexpression or inhibition alter cellular radiosensitivity. Current data indicate the potential of using specific non-coding RNAs as modulators of cellular radiosensitivity to improve outcome of radiotherapy.

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Differences in DNA Repair Capacity, Cell Death and Transcriptional Response after Irradiation between a Radiosensitive and a Radioresistant Cell Line

Cited by 41 publications

References 71 publications

Unmasking Transcriptional Heterogeneity in Senescent Cells

Unmasking Transcriptional Heterogeneity in Senescent Cells

The association of changes in RAD51 and survivin expression levels with the proton beam sensitivity of Capan‑1 and Panc‑1 human pancreatic cancer cells

Non-Coding RNAs in Cancer Radiosensitivity: MicroRNAs and lncRNAs as Regulators of Radiation-Induced Signaling Pathways

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