生物信息学技术在发现增塑剂促进急性骨髓性白血病机制中的应用。

IF 2.1 4区 医学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Yi Zhan, Jiandong Shi
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引用次数: 0

摘要

本研究旨在阐明常用的增塑剂,包括邻苯二甲酸二乙酯(DEP)、邻苯二甲酸二甲酯(DMP)和邻苯二甲酸二辛酯(DOP)在急性髓性白血病(AML)发病机制中的潜在作用。重点是强调这些环境化学物质和参与肿瘤发生的关键分子途径之间的复杂相互作用。我们利用网络毒理学和分子对接技术分析了增塑剂与AML相关关键蛋白之间的相互作用。利用癌症基因组图谱(TCGA)等数据库,我们根据基因表达将AML骨髓样本中选定的关键基因分为两组,并比较它们的生存分析。富集分析确定了与这些基因相关的生物学途径。富集分析强调了增塑剂靶向基因与AML发展的基本途径之间的关联,表明增塑剂对包括血液恶性肿瘤在内的各种癌症具有广泛的影响。随后使用TCGA数据对AML进行表达分析,结果表明这些基因与AML患者的生存具有显著的统计学相关性,证实了它们在肿瘤生物学中的关键作用。本研究提供的证据表明,暴露于增塑剂可能通过与关键蛋白和信号通路的相互作用影响AML的发病机制。通过使用网络药理学和蛋白质相互作用分析,我们的研究结果强调了与增塑剂相关的潜在风险。这些结果强调了进一步的流行病学和临床研究的必要性,以充分了解增塑剂暴露对AML风险的影响,从而为未来的预防和治疗策略提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Application of bioinformatics techniques to discovery of mechanisms by which plasticizers promote acute myelogenous leukemia.

This study aims to elucidate the potential roles of commonly used plasticizers, including Diethyl Phthalate (DEP), Dimethyl Phthalate (DMP), and Dioctyl Phthalate (DOP), in the pathogenesis of Acute Myeloid Leukemia (AML). The focus is to highlight the complex interactions between these environmental chemicals and key molecular pathways involved in tumorigenesis. We employed network toxicology and molecular docking techniques to analyze the interactions between plasticizers and key proteins associated with AML. Utilizing databases such as The Cancer Genome Atlas (TCGA), we divided selected key genes from AML bone marrow samples into two groups based on gene expression and compared their survival analyses. Enrichment analysis was conducted to identify the biological pathways associated with these genes. The enrichment analysis underscored the association between the plasticizer-targeted genes and essential pathways in AML development, indicating a broad impact of plasticizers on various cancers, including hematologic malignancies. Subsequent expression analysis using TCGA data for AML demonstrated that these genes have significant statistical relevance to the survival in AML, confirming their critical roles in tumor biology. This study provides evidence that exposure to plasticizers could influence the pathogenesis of AML through interactions with key proteins and signaling pathways. By utilizing network pharmacology and protein interaction analysis, our findings emphasize the potential risks associated with plasticizers. These results highlight the necessity for further epidemiological and clinical research to fully understand the impact of plasticizer exposure on AML risk, thereby informing future preventive and therapeutic strategies.

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来源期刊
Drug and Chemical Toxicology
Drug and Chemical Toxicology 医学-毒理学
CiteScore
6.00
自引率
3.80%
发文量
99
审稿时长
3 months
期刊介绍: Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal. Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.
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