A comprehensive analysis of metabolomics and transcriptomics reveals new biomarkers and mechanistic insights on DEHP exposures in MCF-7 cells

文献类型： 外文期刊

第一作者： Lu, Yu-Shun

作者： Lu, Yu-Shun;Yao, Gui-Xiao;Wang, Xin-Lu;Liu, Jia-Xi;Qiu, Jing;Li, Yun;Qian, Yong-Zhong;Xu, Yan-Yang;Lu, Yu-Shun;Yao, Gui-Xiao;Liu, Jia-Xi;Yu, Jiang;Qiu, Jing;Li, Yun;Qian, Yong-Zhong;Xu, Yan-Yang

作者机构：

关键词： Metabolomics; Transcriptomics; MCF-7; Proliferation effect; DEHP

期刊名称：CHEMOSPHERE （ 影响因子：7.086； 五年影响因子：6.956 ）

ISSN： 0045-6535

年卷期： 2020 年 255 卷

页码：

收录情况： SCI

摘要： Di-(2-ethylhexyl) phthalate (DEHP) is one of the most important environmental pollutants and affects multiple pathways upon human exposure. DEHP could induce MCF-7 cell proliferation at a very low dose; however, the possible linkage between DEHP and the cell proliferation effect is still unclear. Here, we carried out a comprehensive metabolome and transcriptome analysis to depict the possible molecular mechanisms of the effect of DEHP exposure on MCF-7 proliferation. In this paper, MCF-7 cells treated with DEHP at a dose of 1 mu M for 48 h were selected for metabolome and transcriptome analysis. Untargeted and targeted metabolomics identified 8 differential metabolites, including amino acids, purine, pyrimidine and nucleotides. The metabolite changes were associated with 9 metabolic pathways. Disorders in riboflavin, histidine, beta-alanine metabolism, and nitrogen metabolism caused by DEHP exposure are important concerns for MCF-7 proliferation. Moreover, a transcriptomics study of the MCF-7 cells found a total of 500 differentially expressed genes (DEGs). KEGG enrichment analyses showed that pathways in cancer had stronger responses. The results of integrated analysis of the interactions between the DEGs and metabolites revealed significant changes in the purine metabolism pathway, which will shed light on the mechanism of MCF-7 cell proliferation after DEHP exposure. Overall, this study depicts the possible contribution of DEHP exposure to MCF-7 cell proliferation and highlights the power of omits platforms to deepen the mechanistic understanding of toxicity caused by endocrine disrupting chemicals. (C) 2020 Elsevier Ltd. All rights reserved.

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