Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

Kabacik, Sylwia; Manning, Grainne; Raffy, Claudine; Bouffler, Simon; Badie, Christophe

doi:10.1667/rr13876.1

Cited by 48 publications

(44 citation statements)

References 77 publications

(62 reference statements)

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“…S1) data and because of its proposed role in central cancer pathways such as the p53 network (27). With respect to the latter, TP53TG1 expression is induced in a p53-dependent manner upon conditions of cellular stress that involve the induction of double-strand breaks, such as UV irradiation (27,28), or exposure to bleomycin or cisplatin (28).…”

Section: Resultsmentioning

confidence: 99%

“…p53 is known to activate TP53TG1 expression upon the induction of double-strand breaks in DNA caused by ionizing irradiation (27,28) or treatment with DNA-damaging agents (27). This prompted us to consider whether TP53TG1 hypermethylation-associated silencing in cancer cells affected the sensitivity of chemotherapy drugs that directly target DNA.…”

Section: Tp53tg1 Contributes To P53mentioning

confidence: 99%

“…With the exception of its role as a transcript induced by p53 upon DNA damage (27,28), nothing is known about the functions of TP53TG1. To identify protein partners of TP53TG1 that could characterize its activity in the processes described here, we performed RNA pull-down assays combined with mass spectrometry (MS).…”

Section: Tp53tg1 Binds To the Rna Binding Protein Ybx1 And Prevents Itsmentioning

confidence: 99%

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Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer

Díaz‐Lagares

Crujeiras

López-Serra

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

138

137

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Long noncoding RNAs (lncRNAs) are important regulators of cellular homeostasis. However, their contribution to the cancer phenotype still needs to be established. Herein, we have identified a p53-induced lncRNA, TP53TG1, that undergoes cancer-specific promoter hypermethylation-associated silencing. In vitro and in vivo assays identify a tumor-suppressor activity for TP53TG1 and a role in the p53 response to DNA damage. Importantly, we show that TP53TG1 binds to the multifaceted DNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. TP53TG1 epigenetic inactivation in cancer cells releases the transcriptional repression of YBX1-targeted growth-promoting genes and creates a chemoresistant tumor. TP53TG1 hypermethylation in primary tumors is shown to be associated with poor outcome. The epigenetic loss of TP53TG1 therefore represents an altered event in an lncRNA that is linked to classical tumoral pathways, such as p53 signaling, but is also connected to regulatory networks of the cancer cell.DNA methylation | long noncoding RNA | epigenetics | cancer

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Section: Resultsmentioning

confidence: 99%

Section: Tp53tg1 Contributes To P53mentioning

confidence: 99%

Section: Tp53tg1 Binds To the Rna Binding Protein Ybx1 And Prevents Itsmentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer

Díaz‐Lagares

Crujeiras

López-Serra

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

138

137

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“…This is thought to promote resistance to apoptosis and lymphoma survival. Fas-AS1 is also induced in T lymphocytes in response to ionizing radiation by an ataxia telangiectasia, mutated-dependent mechanism, a critical mediator of the DNA damage response and a sentinel of genomic integrity [83]. Importantly, the RBM5 protein is involved in pre-mRNA to mature mRNA splicing of a number of tumor suppressor genes, including p53.…”

Section: Additional T Cell-associated Lncrnasmentioning

confidence: 99%

Long noncoding RNAs in T lymphocytes

Aune

Crooke

Spurlock

2015

Journal of Leukocyte Biology

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Long noncoding RNAs are recently discovered regulatory RNA molecules that do not code for proteins but influence a vast array of biologic processes. In vertebrates, the number of long noncoding RNA genes is thought to greatly exceed the number of protein-coding genes. It is also thought that long noncoding RNAs drive the biologic complexity observed in vertebrates compared with that in invertebrates. Evidence of this complexity has been found in the T-lymphocyte compartment of the adaptive immune system. In the present review, we describe our current level of understanding of the expression of specific long or large intergenic or intervening long noncoding RNAs during T-lymphocyte development in the thymus and differentiation in the periphery and highlight the mechanisms of action that specific long noncoding RNAs employ to regulate T-lymphocyte function, both in vitro and in vivo.

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“…Over recent years, a greater understanding has been obtained of the transcriptional response in cells and expression of specific genes can depend on radiation dose (11–13), dose rate (14, 15), radiation quality (16), and lapse between stress and analysis (17, 18). The level of dose also plays an important role.…”

Section: Introductionmentioning

confidence: 99%

Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC

et al. 2017

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Ionizing radiation (IR) exposure of cells in vitro and in vivo triggers a complex cellular response among which modifications of gene expression have been consistently reported. Nevertheless, little is currently known about the transcriptionally responsive genes which play a role in the inflammation response. In order to improve our understanding of such transcriptional response to radiation in vivo, we simultaneously monitored the expression of 249 genes associated with the inflammation response over the course of the radiotherapy treatment in blood of patients treated for endometrial or head and neck cancer. We have identified genes whose transcriptional expression is either upregulated (ARG1, BCL2L1) or downregulated (MYC) several fold in vivo. These modifications were consistently detected across patients and further confirmed by quantitative real-time polymerase chain reaction (QRT-PCR); they were specifically significant toward the end of the radiotherapy treatment, 5 weeks following the first radiation fraction and more pronounced in endometrial patients (respectively, 2.9, 4.1, and 1.8 times). Importantly, in an attempt to correlate expression levels with normal tissue reaction to IR, we also identified three other genes CD40, OAS2, and CXCR1 whose expression level fluctuations during radiotherapy were more pronounced in patients developing late normal tissue responses to curative radiotherapy after the end of the radiotherapy treatment. Overall, we identified inflammation-associated genes which are promising biomarkers of IR exposure and susceptibility to radiation-induced toxicity.

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Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

Cited by 48 publications

References 77 publications

Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer

Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer

Long noncoding RNAs in T lymphocytes

Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC

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