Fumonisin B1 inhibits p53-dependent apoptosis via HOXA11-AS/miR-124/DNMT axis in human hepatoma (HepG2) cells

Abstract

Fumonisin B1 (FB1), a mycotoxin, induces toxic and carcinogenic effects in humans and animals by influencing the epigenome. The lncRNA, homeobox A11 antisense (HOXA11-AS) modulates DNA methylation and functions as a competing endogenous RNA or molecular scaffold. However, the role of HOXA11-AS in FB1-toxicity is unknown. Therefore, we investigated the effect of FB1 on p53-dependent apoptosis via the HOXA11-AS/miR-124/DNMT axis. HepG2 cells were treated with various concentrations of FB1 (0, 5, 50, 100, and 200 µM; 24 h). Qualitative polymerase chain reaction and/or western blot were used to determine the expression of HOXA11-AS, miR-124, SP1, DNMT3B, and p53. The OneStep qMethyl Kit was used to assess p53 promoter methylation, while luminometry was used to measure caspase activity. FB1 upregulated HOXA11-AS, leading to a subsequent decrease in miR-124 and increases in SP1 and DNMT3B. This promoted hypermethylation of p53 promoters, thereby reducing p53 expression and caspase activity. Taken together, the data suggest that FB1 inhibits p53-dependent apoptosis via the HOXA11-AS/miR-124/DNMT axis in HepG2 cells.