Radiation damage to normal tissues is a serious concern. P53 is a well-known transcription factor which is closely associated with radiation-induced cell damage. Increasing evidence has indicated that regulation of metabolism by p53 represents a reviving mechanism vital to protect cell survival. We aimed to explore the interactions of radiation-induced transcripts with the cellular metabolism regulated by p53. Human bronchial epithelial (HBE) cell line was used to knockout p53 using CRISPR/cas9. Transcriptomic analysis was conducted by microarray and metabolomic analysis was conducted by GC–MS. Integrative omics was performed using MetaboAnalyst. 326 mRNAs showed significantly altered expression in HBE p53-/- cells post-radiation, of which 269 were upregulated and 57 were downregulated. A total of 147 metabolites were altered, including 45 that increased and 102 that decreased. By integrated analysis of both omic data, we found that in response to radiation insult, nitrogen metabolism, glutathione metabolism, arachidonic acid metabolism, and glycolysis or gluconeogenesis may be dysregulated due to p53. Our study provided a pilot comprehensive view of the metabolism regulated by p53 in response to radiation exposure. Detailed evaluation of these important p53-regulated metabolic pathways, including their roles in the response to radiation of cells, is essential to elucidate the molecular mechanisms of radiation-induced damage.

中文翻译：

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转录组学和代谢组学分析的综合分析揭示了 HBE 细胞对电离辐射反应的 p53 相关途径。

对正常组织的辐射损伤是一个严重的问题。P53 是一种众所周知的转录因子，与辐射诱导的细胞损伤密切相关。越来越多的证据表明，p53 对代谢的调节代表了一种对保护细胞存活至关重要的恢复机制。我们旨在探索辐射诱导的转录物与 p53 调节的细胞代谢的相互作用。人支气管上皮 (HBE) 细胞系用于使用 CRISPR/cas9 敲除 p53。通过微阵列进行转录组学分析，通过GC-MS进行代谢组学分析。使用 MetaboAnalyst 进行综合组学。326 种 mRNA 在放射后 HBE p53-/- 细胞中的表达显着改变，其中 269 种上调，57 种下调。总共改变了 147 种代谢物，其中增加了45个，减少了102个。通过对这两个组学数据的综合分析，我们发现在对辐射损伤的反应中，氮代谢、谷胱甘肽代谢、花生四烯酸代谢和糖酵解或糖异生可能因 p53 而失调。我们的研究提供了一个由 p53 调节以响应辐射暴露的代谢的初步综合视图。详细评估这些重要的 p53 调节代谢途径，包括它们在细胞辐射反应中的作用，对于阐明辐射诱导损伤的分子机制至关重要。p53 可能导致糖酵解或糖异生失调。我们的研究提供了一个由 p53 调节以响应辐射暴露的代谢的初步综合视图。详细评估这些重要的 p53 调节代谢途径，包括它们在细胞辐射反应中的作用，对于阐明辐射诱导损伤的分子机制至关重要。p53 可能导致糖酵解或糖异生失调。我们的研究提供了一个由 p53 调节以响应辐射暴露的代谢的初步综合视图。详细评估这些重要的 p53 调节代谢途径，包括它们在细胞辐射反应中的作用，对于阐明辐射诱导损伤的分子机制至关重要。