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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\u2010throughput sequencing. The gene and miRNA expression results showed that 2547 genes and 315 miRNAs were changed in the AFB1\u2010treated group compared with the DMSO group. Among them, <jats:italic>RSAD2<\/jats:italic> and <jats:italic>SCIN<\/jats:italic> were significantly upregulated, whereas <jats:italic>TRAPPC3L<\/jats:italic> and <jats:italic>UBE2L6<\/jats:italic> were significantly downregulated. Has\u2010miR\u201033b\u20103p was significantly upregulated, whereas Has\u2010miR\u20103613\u20105p 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 of <jats:italic>DNMT3a<\/jats:italic> and <jats:italic>DNMT3b<\/jats:italic> was significantly upregulated. Moreover, hypermethylation occurred in <jats:italic>TRAPPC3L<\/jats:italic>, <jats:italic>CDH13<\/jats:italic>, and <jats:italic>SPINK13<\/jats:italic>. 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\u2010miR\u20103613\u20105p, Hsa\u2010miR\u2010615\u20105p, Hsa\u2010miR\u2010615\u20103p, and Hsa\u2010miR\u20103158\u20103p were the key miRNAs for malignant transformation of L02 cells induced by AFB1. In addition, the expression of <jats:italic>ONECUT2<\/jats:italic>, <jats:italic>RAP1GAP2<\/jats:italic>, and <jats:italic>FSTL4<\/jats:italic> was regulated by DNA methylation and miRNAs. These results suggested that the gene expression network regulated by DNA methylation and miRNAs may play a vital role in AFB1\u2010induced hepatocellular carcinoma.<\/jats:p>","DOI":"10.1002\/jat.4233","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T02:40:21Z","timestamp":1632537621000},"page":"475-489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Gene expression network related to DNA methylation and miRNA regulation during the process of aflatoxin B1\u2010induced malignant transformation of L02 cells"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5877-264X","authenticated-orcid":false,"given":"Ji","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Toxicology, College of Preventive Medicine Third Military Medical University (Army Medical University)  Chongqing China"},{"name":"School of Public Healthy and 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