Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 toward Intestinal NCM460 Cells
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, pr...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/14/6/368 |
| _version_ | 1827656239125889024 |
|---|---|
| author | Ya-Nan Gao Xue Yang Jia-Qi Wang Hui-Min Liu Nan Zheng |
| author_facet | Ya-Nan Gao Xue Yang Jia-Qi Wang Hui-Min Liu Nan Zheng |
| author_sort | Ya-Nan Gao |
| collection | DOAJ |
| description | 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 μM) and AFM1 (5–20 μM) 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 μM) and AFM1 (2.5 μM) 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. |
| first_indexed | 2024-03-09T22:18:50Z |
| format | Article |
| id | doaj.art-07f79931970941328e5e1e7b4fe8656f |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T22:18:50Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-07f79931970941328e5e1e7b4fe8656f2023-11-23T19:16:46ZengMDPI AGToxins2072-66512022-05-0114636810.3390/toxins14060368Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 toward Intestinal NCM460 CellsYa-Nan Gao0Xue Yang1Jia-Qi Wang2Hui-Min Liu3Nan Zheng4Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaAflatoxin 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 μM) and AFM1 (5–20 μM) 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 μM) and AFM1 (2.5 μM) 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.https://www.mdpi.com/2072-6651/14/6/368aflatoxin B1aflatoxin M1additive effectsmulti-omics analyses |
| spellingShingle | Ya-Nan Gao Xue Yang Jia-Qi Wang Hui-Min Liu Nan Zheng Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 toward Intestinal NCM460 Cells Toxins aflatoxin B1 aflatoxin M1 additive effects multi-omics analyses |
| title | Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 toward Intestinal NCM460 Cells |
| title_full | Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 toward Intestinal NCM460 Cells |
| title_fullStr | Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 toward Intestinal NCM460 Cells |
| title_full_unstemmed | Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 toward Intestinal NCM460 Cells |
| title_short | Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 toward Intestinal NCM460 Cells |
| title_sort | multi omics reveal additive cytotoxicity effects of aflatoxin b1 and aflatoxin m1 toward intestinal ncm460 cells |
| topic | aflatoxin B1 aflatoxin M1 additive effects multi-omics analyses |
| url | https://www.mdpi.com/2072-6651/14/6/368 |
| work_keys_str_mv | AT yanangao multiomicsrevealadditivecytotoxicityeffectsofaflatoxinb1andaflatoxinm1towardintestinalncm460cells AT xueyang multiomicsrevealadditivecytotoxicityeffectsofaflatoxinb1andaflatoxinm1towardintestinalncm460cells AT jiaqiwang multiomicsrevealadditivecytotoxicityeffectsofaflatoxinb1andaflatoxinm1towardintestinalncm460cells AT huiminliu multiomicsrevealadditivecytotoxicityeffectsofaflatoxinb1andaflatoxinm1towardintestinalncm460cells AT nanzheng multiomicsrevealadditivecytotoxicityeffectsofaflatoxinb1andaflatoxinm1towardintestinalncm460cells |