ArticleToxicological sciences : an official journal of the Society of Toxicology2017
Sex-Differential Responses of Tumor Promotion-Associated Genes and Dysregulation of Novel Long Noncoding RNAs in Constitutive Androstane Receptor-Activated Mouse Liver.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Single Nucleus MultiOmics Links Novel Transcription Factor Motifs to Murine Hepatic Sex Differences in Chromatin Accessibility and Metabolic Dysfunction-Associated Steatotic Liver Disease.bioRxiv : the preprint server for biology · 2025Article
- Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparity.BMC cancer · 2025Article
- HDI-STARR-seq: Condition-specific enhancer discovery in mouse liver in vivo.BMC genomics · 2024Article
- Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: primary and secondary gene responses with links to disease progression.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- HDI-STARR-seq: Condition-specific enhancer discovery in mouse liver in vivo.bioRxiv : the preprint server for biology · 2024Article
- Pharmacological activation of constitutive androstane receptor induces female-specific modulation of hepatic metabolism.JHEP reports : innovation in hepatology · 2024Article
- TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule.Toxicology and applied pharmacology · 2023Article
- Dysregulation of murine long noncoding single-cell transcriptome in nonalcoholic steatohepatitis and liver fibrosis.RNA (New York, N.Y.) · 2023Article
- Review
- Constitutive Androstane Receptor Agonist, TCPOBOP: Maternal Exposure Impairs the Growth and Development of Female Offspring in Mice.International journal of molecular sciences · 2023Article
- TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule.bioRxiv : the preprint server for biology · 2023Article
- Inflammasome and pyroptosis in autoimmune liver diseases.Frontiers in immunology · 2023Review
- Long non-coding RNA G23Rik attenuates fasting-induced lipid accumulation in mouse liver.Molecular and cellular endocrinology · 2022Article
- Interplay Between GH-regulated, Sex-biased Liver Transcriptome and Hepatic Zonation Revealed by Single-Nucleus RNA Sequencing.Endocrinology · 2022Article
- Impact of Neonatal Activation of Nuclear Receptor CAR (Nr1i3) on Cyp2 Gene Expression in Adult Mouse Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Constitutively Active STAT5b Feminizes Mouse Liver Gene Expression.Endocrinology · 2022Article
- Diverse MicroRNAs-mRNA networks regulate the priming phase of mouse liver regeneration and of direct hyperplasia.Cell proliferation · 2022Article
- Harnessing natural variation to identify cis regulators of sex-biased gene expression in a multi-strain mouse liver model.PLoS genetics · 2021Article
- Non-coding RNA crosstalk with nuclear receptors in liver disease.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Xenobiotic agonists of constitutive androstane receptor (CAR) induce many hepatic drug metabolizing enzymes, but following prolonged exposure, promote hepatocellular carcinoma, most notably in male mouse liver. Here, we used nuclear RNA-seq to characterize global changes in the mouse liver transcriptome following exposure to the CAR-specific agonist ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), including changes in novel long noncoding RNAs that may contribute to xenobiotic-induced pathophysiology. Protein-coding genes dysregulated by 3 h TCPOBOP exposure were strongly enriched in KEGG pathways of xenobiotic and drug metabolism, with stronger and more extensive gene responses observed in female than male liver. After 27 h TCPOBOP exposure, the number of responsive genes increased >8-fold in males, where the top enriched pathways and their upstream regulators expanded to include factors implicated in cell cycle dysregulation and hepatocellular carcinoma progression (cyclin-D1, oncogenes E2f, Yap, Rb, Myc, and proto-oncogenes β-catenin, FoxM1, FoxO1, all predicted to be activated by TCPOBOP in male but not female liver; and tumor suppressors p21 and p53, both predicted to be inhibited). Upstream regulators uniquely associated with 3 h TCPOBOP-exposed females include TNF/NFkB pathway members, which negatively regulate CAR-dependent proliferative responses and may contribute to the relative resistance of female liver to TCPOBOP-induced tumor promotion. These responses may be modified by the many long noncoding liver RNAs we show are dysregulated by TCPOBOP or pregnane-X-receptor agonist exposure, including lncRNAs proximal to CAR target genes Cyp2b10, Por, and Alas1. These data provide a comprehensive view of the CAR-regulated transcriptome and give insight into the mechanism of sex-biased susceptibility to CAR-dependent mouse liver tumorigenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.