Being a hydroxylated metabolite of aflatoxin B1 (AFB1) and the most threatening aspect of AFB1 contamination, aflatoxin M1 (AFM1) can lead to hepatotoxicity and hepato-carcinogenicity, and possess intestinal cytotoxicity. However, little is known about the potential mechanisms of the extrahepatic effect. The aim of this study was to investigate intestinal dysfunction induced by AFM1 via transcriptome analysis. Gene expression profiling was analyzed to comparatively characterize the differentially expressed genes (DEGs) after differentiated Caco-2 cells were exposed to different concentrations of AFM1 for 48 h. A total of 165 DEGs were significantly clustered into two down-regulated patterns. Protein-protein interaction (PPI) network analysis based on Search Tool for Retrieval of Interacting Genes (STRING)suggested that 23 key enzymes mainly participated in the regulation of the cell cycle. Q-PCR analysis was performed to validate that key 12 genes (BUB1, BUB1B, MAD2L1, CCNA2, RB1, CDK1, ANAPC4, ATM, KITLG, PRKAA2, SIRT1, and SOS1) were involved. This study firstly revealed that the toxicity of AFM1 to intestinal functions may be partly due to the occurrence of cell cycle arrest, which is linked to changes in CDK1, SOS1/Akt, and AMPK signaling molecules.
Keywords: Aflatoxin M1; Cell cycle; Intestinal dysfunction.
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