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首页> 外文期刊>EBioMedicine >The Transcriptional Landscape of p53 Signalling Pathway
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The Transcriptional Landscape of p53 Signalling Pathway

机译：p53信号通路的转录景观

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Although recent cancer genomics studies have identified a large number of genes that were mutated in human cancers, p53 remains as the most frequently mutated gene. To further elucidate the p53-signalling network, we performed transcriptome analysis on 24 tissues in p53^+^/^+ or p53^-^/^- mice after whole-body X-ray irradiation. Here we found transactivation of a total of 3551 genes in one or more of the 24 tissues only in p53^+^/^+ mice, while 2576 genes were downregulated. p53 mRNA expression level in each tissue was significantly associated with the number of genes upregulated by irradiation. Annotation using TCGA (The Cancer Genome Atlas) database revealed that p53 negatively regulated mRNA expression of several cancer therapeutic targets or pathways such as BTK, SYK, and CTLA4 in breast cancer tissues. In addition, stomach exhibited the induction of Krt6, Krt16, and Krt17 as well as loricrin, an epidermal differentiation marker, after the X-ray irradiation only in p53^+^/^+ mice, implying a mechanism to protect damaged tissues by rapid induction of differentiation. Our comprehensive transcriptome analysis elucidated tissue specific roles of p53 and its signalling networks in DNA-damage response that will enhance our understanding of cancer biology.
机译：尽管最近的癌症基因组学研究已经确定了在人类癌症中大量突变的基因，但p53仍然是最常见的突变基因。为了进一步阐明p53信号网络，我们在全身X射线照射后对p53 ^ + ^ / ^ +或p53 ^-^ / ^-小鼠的24个组织进行了转录组分析。在这里，我们发现仅在p53 ^ + ^ / ^ +小鼠中，在24个组织中的一个或多个组织中，共有3551个基因被反式激活，而2576个基因被下调。每个组织中的p53 mRNA表达水平与辐射上调的基因数量显着相关。使用TCGA（癌症基因组图谱）数据库的注释显示，p53在乳腺癌组织中负调控了几种癌症治疗靶标或途径（如BTK，SYK和CTLA4）的mRNA表达。此外，仅在p53 ^ + ^ / ^ +小鼠中进行X射线照射后，胃对Krt6，Krt16和Krt17以及表皮分化标记物洛瑞林有诱导作用，这暗示了通过快速保护受损组织的机制诱导分化。我们全面的转录组分析阐明了p53及其信号网络在DNA损伤反应中的组织特异性作用，这将增进我们对癌症生物学的理解。

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