Upregulation of miR-34a-5p antagonizes AFB1-induced genotoxicity in F344 rat liver

摘要: Aflatoxin B1 (AFB1) is a well-known human hepatotoxicant and genotoxicant. Recent studies demonstrated that aberrant miRNA expression patterns were correlated with the cellular genetic lesions induced by chemicals. To explore role of miRNAs in AFB1-induced hepatotoxicity genotoxicity, we examined alterations F334 rat livers after exposure to 100 μg/kg or 200 AFB1 for 28 days. Using high-throughput sequencing, discovered rno-miR-34a-5p, rno-miR-200b-3p, rno-miR-429 up-regulated rno-miR-130a-3p was down-regulated liver tissue from rats received AFB1; this finding validated real-time PCR. treatment resulted upregulation rno-miR-34a-5p rno-miR-200b-3p H-4-II-E cell line similar our vivo observations. Moreover, transcriptionally elevated via p53 activation exposure. Upregulation suppressed cycle-related genes CCND1, CCNE2 MET led cycle arrest G0-G1 phase. The CBMN assay indicated inhibition aggravated DNA damage AFB1, which might be associated shortening repair period. Circulating miR-34a-5p sera preceded significant increase ALT activity other group. These observations responded sensitively facilitated impacting cycle. Thus, circulating may sensitive indicator induction hepatic genotoxicity rats.