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首页> 外文期刊>International Journal of Environmental Research and Public Health >The Aryl Hydrocarbon Receptor Pathway: A Key Component of the microRNA-Mediated AML Signalisome
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The Aryl Hydrocarbon Receptor Pathway: A Key Component of the microRNA-Mediated AML Signalisome

机译：芳烃受体途径：microRNA介导的AML信号体的关键组成部分。

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Recent research has spotlighted the role of microRNAs (miRNAs) as critical epigenetic regulators of hematopoietic stem cell differentiation and leukemia development. Despite the recent advances in knowledge surrounding epigenetics and leukemia, the mechanisms underlying miRNAs’ influence on leukemia development have yet to be clearly elucidated. Our aim was to identify high ranking biological pathways altered at the gene expression level and under epigenetic control. Specifically, we set out to test the hypothesis that miRNAs dysregulated in acute myeloid leukemia (AML) converge on a common pathway that can influence signaling related to hematopoiesis and leukemia development. We identified genes altered in AML patients that are under common regulation of seven key miRNAs. By mapping these genes to a global interaction network, we identified the “AML Signalisome”. The AML Signalisome comprises 53 AML-associated molecules, and is enriched for proteins that play a role in the aryl hydrocarbon receptor (AhR) pathway, a major regulator of hematopoiesis. Furthermore, we show biological enrichment for hematopoiesis-related proteins within the AML Signalisome. These findings provide important insight into miRNA-regulated pathways in leukemia, and may help to prioritize targets for disease prevention and treatment.
机译：最近的研究已经聚焦了microRNA（miRNA）作为造血干细胞分化和白血病发展的关键表观遗传调控因子的作用。尽管关于表观遗传学和白血病的知识最近有所发展，但尚未明确阐明miRNA对白血病发展的影响机制。我们的目的是鉴定在基因表达水平和表观遗传控制下改变的高级生物途径。具体而言，我们着手测试以下假设：在急性髓细胞性白血病（AML）中失调的miRNA会在一条通用途径上汇聚，该途径可能会影响与造血和白血病发展有关的信号传导。我们鉴定了在AML患者中改变的基因，这些基因在七个关键miRNA的共同调控下。通过将这些基因定位到全球相互作用网络，我们确定了“ AML Signalisome”。 AML Signalisome包含53个与AML相关的分子，并富含在芳烃受体（AhR）途径（造血的主要调节剂）中起作用的蛋白质。此外，我们显示了AML Signalisome中与造血相关蛋白的生物富集。这些发现提供了对白血病中miRNA调控途径的重要见解，并可能有助于确定疾病预防和治疗目标的优先级。

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