p53 信号通路与结直肠癌：下游 p53 靶基因与 miRNA 之间的相互作用。
The p53-signaling pathway and colorectal cancer: Interactions between downstream p53 target genes and miRNAs.
机构信息
Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT, United States.
Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT, United States.
出版信息
Genomics. 2019 Jul;111(4):762-771. doi: 10.1016/j.ygeno.2018.05.006. Epub 2018 Jun 1.
INTRODUCTION
We examined expression of genes in the p53-signaling pathway. We determine if genes that have significantly different expression in carcinoma tissue compared to normal mucosa also have significantly differentially expressed miRNAs. We utilize a sample of 217 CRC cases.
METHODS
We focused on fold change (FC) > 1.50 or <0.67 for genes and miRNAs, that were statistically significant after adjustment for multiple comparisons. We evaluated the linear association between the differential expression of miRNA and mRNA. miRNA:mRNA seed-region matches also were determined.
RESULTS
Eleven dysregulated genes were associated with 37 dysregulated miRNAs; all were down-stream from the TP53 gene. MiR-150-5p (HR = 0.82) and miR-196b-5p (HR 0.73) significantly reduced the likelihood of dying from CRC when miRNA expression increased in rectal tumors.
CONCLUSIONS
Our data suggest that activation of p53 from cellular stress, could target downstream genes that in turn could influence cell cycle arrest, apoptosis, and angiogenesis through mRNA:miRNA interactions.
简介
我们研究了 p53 信号通路中基因的表达。我们确定与正常黏膜相比，在癌组织中表达差异显著的基因是否也具有显著差异表达的 miRNA。我们利用了 217 例 CRC 病例的样本。
方法
我们主要关注基因和 miRNA 的倍数变化（FC）＞1.50 或＜0.67，这些基因和 miRNA 在经过多次比较调整后具有统计学意义。我们评估了 miRNA 和 mRNA 之间差异表达的线性关联。还确定了 miRNA:mRNA 种子区域匹配。
结果
11 个失调基因与 37 个失调 miRNA 相关；所有基因都位于 TP53 基因的下游。当直肠肿瘤中 miRNA 表达增加时，miR-150-5p（HR=0.82）和 miR-196b-5p（HR 0.73）显著降低了结直肠癌死亡的可能性。
结论
我们的数据表明，细胞应激激活 p53 后，可能会靶向下游基因，这些基因反过来可能通过 mRNA:miRNA 相互作用影响细胞周期停滞、细胞凋亡和血管生成。
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