Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 toward Intestinal NCM460 Cells

文献类型： 外文期刊

第一作者： Gao, Ya-Nan

作者： Gao, Ya-Nan;Yang, Xue;Wang, Jia-Qi;Liu, Hui-Min;Zheng, Nan;Gao, Ya-Nan;Yang, Xue;Wang, Jia-Qi;Liu, Hui-Min;Zheng, Nan;Gao, Ya-Nan;Yang, Xue;Wang, Jia-Qi;Liu, Hui-Min;Zheng, Nan;Gao, Ya-Nan;Yang, Xue;Wang, Jia-Qi;Liu, Hui-Min;Zheng, Nan

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关键词： aflatoxin B1; aflatoxin M1; additive effects; multi-omics analyses

期刊名称：TOXINS （ 影响因子：5.075； 五年影响因子：5.305 ）

ISSN：

年卷期： 2022 年 14 卷 6 期

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收录情况： SCI

摘要： Aflatoxin B1 (AFB1) is a common crop contaminant, while aflatoxin M1 (AFM1) is implicated in milk safety. Humans are likely to be simultaneously exposed to AFB1 and AFM1; however, studies on the combined interactive effects of AFB1 and AFM1 are lacking. To fill this knowledge gap, transcriptomic, proteomic, and microRNA (miRNA)-sequencing approaches were used to investigate the toxic mechanisms underpinning combined AFB1 and AFM1 actions in vitro. Exposure to AFB1 (1.25-20 mu M) and AFM1 (5-20 mu M) for 48 h significantly decreased cell viability in the intestinal cell line, NCM460. Multi-omics analyses demonstrated that additive toxic effects were induced by combined AFB1 (2.5 mu M) and AFM1 (2.5 mu M) in NCM460 cells and were associated with p53 signaling pathway, a common pathway enriched by differentially expressed mRNAs/proteins/miRNAs. Specifically, based on p53 signaling, cross-omics showed that AFB1 and AFM1 reduced NCM460 cell viability via the hsa-miR-628-3p- and hsa-miR-217-5p-mediated regulation of cell surface death receptor (FAS), and also the hsa-miR-11-y-mediated regulation of cyclin dependent kinase 2 (CDK2). We provide new insights on biomarkers which reflect the cytotoxic effects of combined AFB1 and AFM1 toxicity.

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