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

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

PROVIDER: PRJNA1044785 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26942200_1.fastq.gz	Fastqsanger.gz
	SRR26942200_2.fastq.gz	Fastqsanger.gz
	SRR26942201_1.fastq.gz	Fastqsanger.gz
	SRR26942201_2.fastq.gz	Fastqsanger.gz
	SRR26942202_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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Project description:In rodent models, phthalate exposure alters both the fetal and pubertal testis, but the resulting histopathological changes are divergent. This suggests that the underlying molecular and cellular phthalate mechanism may be age-dependent. Using genome-wide expression profiling of acutely-exposed rats, the initial molecular response in pubertal rat testis following in vivo phthalate exposure was determined. For this study, postnatal day 28 rats were exposed to a single dose of 1 g/kg mono-(2-ethyl)hexyl phthalate (MEHP) and assayed at 1, 2, 3, 6, and 12 hrs thereafter using Affymetrix Rat Genome 230 2.0 Arrays. Experiment Overall Design: At each timepoint, testes from 3 treated and 3 control (corn oil gavage) were analzyed.

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