Gene expression network related to DNA methylation and miRNA regulation during the process of aflatoxin B1 ‐induced malignant transformation of L02 cells

AbstractAflatoxin is a secondary metabolite secreted byAspergillus flavus, parasiticAspergillus, and other fungi through the polyketone pathway, and it can be detected in many foods. Aflatoxin has strong toxicity and carcinogenicity, and many studies have shown that aflatoxin is highly associated with liver cancer. In the present study, malignant transformation of L02 cells was induced by aflatoxin B1 (AFB1), and the gene expression, miRNA expression, and methylation level were detected by high-throughput sequencing. The gene and miRNA expression results showed that 2547 genes and 315 miRNAs were changed in the AFB1-treated group compared with the DMSO group. Among them,RSAD2 andSCIN were significantly upregulated, whereasTRAPPC3L andUBE2L6 were significantly downregulated. Has-miR-33b-3p was significantly upregulated, whereas Has-miR-3613-5p was significantly downregulated. The methylation results showed that 2832 CpG sites were methylated on the promoter or coding DNA sequence (CDS) of the gene, whereas the expression ofDNMT3a andDNMT3b was significantly upregulated. Moreover, hypermethylation occurred inTRAPPC3L,CDH13, andSPINK13. The results of GO and KEGG pathway analyses showed that significantly changed genes and miRNAs were mainly involved in tumor formation, proliferation, invasion, and migration. The results of network map analysis showed that Hsa-miR-3613-5p, Hsa-miR-615-5p, Hsa-miR-615-3p, and Hsa-miR-3158-3p were the key miRNAs for malignant transformation of L02...
Source: Journal of Applied Toxicology - Category: Toxicology Authors: Tags: RESEARCH ARTICLE Source Type: research