Environmental monobutyl phthalate exposure promotes liver cancer via reprogramming cholesterol metabolism and activation of the IRE1α-XBP1s pathway. Environmental monobutyl phthalate exposure promotes liver cancer via reprogramming cholesterol metabolism and activation of the IRE1α-XBP1s pathway

In this study, we applied a long-term cell culture model by treating the liver cancer cell HepG2 and normal hepatocyte L02 to environmental dosage of monobutyl phthalate (MBP), the main metabolite of phthalates. By RNA-seq, ATAC-seq and CUT&Tag-seq analysis, we found that long-term MBP exposure triggered reprogramming of lipid metabolism in HepG2 cells, which was causal to the activation of the IRE1α-XBP1s axis of the unfolded protein response. Furthermore, the XBP1s-regulated gene sets and pathways contributed to the increased aggressiveness of HepG2 cells. Overall design: RNA-seq, ATAC-seq and CUT&Tag-seq analysis upon a long-term cell culture model mimicking chronic MBP exposure.