Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury

Li, Weihong; Zhou, Shixiang; Meng, Jian; Li, Xiaoxin; Li, Lin; Wang, Qi; Qi, Zhenhua; Zhou, Pingkun; Li, Yaqiong; Wang, Zhidong

doi:10.3390/life12010099

Cited by 6 publications

(5 citation statements)

References 71 publications

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“…Particularly, gamma-glutamyl transferase 1 [GGT1], Phospholipase A2G [PLA2], post-transcriptional gene silencing [PTGS], glutathione peroxidase 6 [GPX6], aldolase, fructose-bisphosphate A [ALDOA], acyl-CoA synthetase short chain family member 2 [ACSS2], aldehyde dehydrogenase 3 family member A1 [ALDH3A1], and gamma-glutamyl transferase 6 [GGT6], involved in nitrogen metabolism, glutathione metabolism, glycolysis, or glycogenesis, and arachidonic acid metabolism, were suggested to be regulated by p53 [ 211 ]. DDB2, AEN, TP53 regulated inhibitor of apoptosis (TRIAP1), and TRAF4, which are all downstream of p53, are potential biomarkers within the first 24 h after radiation exposure [ 214 ].…”

Section: P53 As a Biomarker After Irradiationmentioning

confidence: 99%

Role of p53 in Regulating Radiation Responses

Okazaki

2022

Life

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p53 is known as the guardian of the genome and plays various roles in DNA damage and cancer suppression. The p53 gene was found to express multiple p53 splice variants (isoforms) in a physiological, tissue-dependent manner. The various genes that up- and down-regulated p53 are involved in cell viability, senescence, inflammation, and carcinogenesis. Moreover, p53 affects the radioadaptive response. Given that several studies have already been published on p53, this review presents its role in the response to gamma irradiation by interacting with MDM2, NF-κB, and miRNA, as well as in the inflammation processes, senescence, carcinogenesis, and radiation adaptive responses. Finally, the potential of p53 as a biomarker is discussed.

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Section: P53 As a Biomarker After Irradiationmentioning

confidence: 99%

Role of p53 in Regulating Radiation Responses

Okazaki

2022

Life

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“…Therefore, Repairable DNA damage is normally transient, whereas P53 activation causes cells to initiate an apoptotic pathway (Ragunathan et al, 2020). Another study reported that P53 can be use as biodosimitry marker to demonstrate the radiosensitivity in early exposure within 24 h after IR exposure (Li et al, 2022). P53 is an important tumor suppressor gene that is expressed at low levels in cells, when cells are exposed to stress-induced stimulation, the expression of p53 increases, preventing genome destruction, which assist in maintaining cell stability and preventing cancer development (Kong et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylated P53 (TP53) in Cancer Patients Undergoing Radiotherapy

2023

JPRD

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Introduction: Cancer is a common disease worldwide, and radiotherapy is an important option for cancer treatment. P53 tumour suppressor has a role in apoptosis and cancer treatment response. P53 is phosphorylated in response to ionizing radiation by kinases of the ataxia telangiectasia mutation family (ATM). The aim of this study was to detect the DND damage response in cancer patients before and after radiation therapy through measurements the expression levels of phosphorylated P53 on T18. Material and Methods: Total of 28 cancer patients on radiotherapy were participate in this study to collect blood samples pre and post radiotherapy compared to 28 healthy people matched in age and sex as control group. P53 antibody used against Phospho-p53 (T18) was obtained from CUSABIO using enzyme linked immunosorbent assay (ELISA). Results: 21 of patients were breast cancer, and 7 of patients were Head and Neck. 6 male and 22 female. Median of age was 44 years old. Median of body mass index (BMI) for breast cancer patients was 30 while BMI for head and neck was 23. The absorbed dose for breast cancer was 40.5Gy. While the doses for Head and neck cancers were between 20Gy- 66Gy. Phosphorylated P53 expression increased significantly (P= <0.0001) in the patients preradiotherapy compared to the control group. While no significant difference observed between preradiotherapy and postradiotherapy groups (P=0.7). Individually, 19 patients showed increased in phosphorylated P53 expression postradiotherapy, while, nine patients were showed low P53 postradiotherapy, 8 of them diagnosed with breast cancer and 1 diagnosed with Oesophagus. Conclusion: phosphorylated on T18 can be consider a predictive marker for cancer. Phosphorylated P53 can be indict the DNA damage and response through its activation and proapoptotic effects. Protein expression such as P53 can be use as biomarker to demonstrate individual radiation sensitivity in cancer patients.

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“…Furthermore, the integration of data from multiple cohorts is essential to generate robust and reproducible results (Beuchel et al, 2021). Here, we detected 20 radio-responsive genes and 17 of these 20 genes (i.e., APOBEC3H, ASCC3, DDB2, E2F7, FDXR, FHL2, GADD45, LIG1, MDM2, PCNA, PHPT1, POLH, RPS27L, SLC4A11, TNFSF4, VWCE, and ZNF79) have been previously identified as IR responsive genes (Kang et al, 2003;Dressman et al, 2007;Fachin et al, 2007;Gruel et al, 2008;Meadows et al, 2008;Paul and Amundson, 2008;Henríquez Hernández et al, 2009;Kabacik et al, 2011;Mayer et al, 2011;Pogosova-Agadjanyan et al, 2011;Templin et al, 2011;Wen et al, 2011;Boldt et al, 2012;Knops et al, 2012;El-Saghire et al, 2013;Nosel et al, 2013;Paul et al, 2013;Versteyhe et al, 2013;Beer et al, 2014;Vinoth et al, 2014;Ghandhi et al, 2015;Macaeva et al, 2016;Rouchka et al, 2016;Broustas et al, 2017;Lacombe et al, 2018;Piotto et al, 2018;Ghandhi et al, 2019;Cruz-Garcia et al, 2020a;Cruz-Garcia et al, 2020b;Li et al, 2022). Two of the three remaining DEGs (i.e., CCL27 and GLS2) have also been described in the context of DNA damage or of oxidative stress, which is also related to radiation as radiationinduced reactive oxygen species (ROS).…”

Section: Figurementioning

confidence: 92%

A workflow for the creation of regulatory networks integrating miRNAs and lncRNAs associated with exposure to ionizing radiation using open source data and tools

Freiesleben

Unverricht-Yeboah²,

Gütebier³

et al. 2022

Front. Syst. Biol.

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MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are involved in the modulation of the DNA-damage response (DDR) and upon exposure to ionizing radiation (IR), their expression fluctuates. In this study, we propose a workflow that enables the creation of regulatory networks by integrating transcriptomics data as well as regulatory data in order to better understand the interplay between genes, transcription factors (TFs), miRNAs, and lncRNAs in the cellular response to IR. We preprocessed and analyzed publicly available gene expression profiles and then applied our consensus and integration approach using open source data and tools. To exemplify the benefits of our proposed workflow, we identified a total of 32 differentially expressed transcripts corresponding to 20 unique differentially expressed genes (DEGs) and using these DEGs, we constructed a regulatory network consisting of 106 interactions and 100 nodes (11 DEGs, 78 miRNAs, 1 DEG acting as a TF, and 10 lncRNAs). Overrepresentation analyses (ORAs) furthermore linked our DEGs and miRNAs to annotations pertaining to the DDR and to IR. Our results show that MDM2 and E2F7 function as network hubs, and E2F7, miR-25-3p, let-7a-5p, and miR-497-5p are the four nodes with the highest betweenness centrality. In brief, our workflow, that is based on open source data and tools, and that generates a regulatory network, provides novel insights into the regulatory mechanisms involving miRNAs and lncRNAs in the cellular response to IR.

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Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury

Cited by 6 publications

References 71 publications

Role of p53 in Regulating Radiation Responses

Role of p53 in Regulating Radiation Responses

Phosphorylated P53 (TP53) in Cancer Patients Undergoing Radiotherapy

A workflow for the creation of regulatory networks integrating miRNAs and lncRNAs associated with exposure to ionizing radiation using open source data and tools

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