Copy Number Gains of VPS72 Drive De Novo Lipogenesis and Hepatocarcinogenesis via ATF3/mTORC1/SREBP1 Axis DOI Creative Commons
Qinglin Zhang, Yunxing Huang, Yin Tong

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and a major contributor to cancer-related mortality globally. Central its pathogenesis dysregulation lipid metabolism in hepatocytes, leading abnormal accumulation. Our bioinformatics analysis has identified histone acetyltransferase complex subunit VPS72 as being associated with HCC, yet precise molecular mechanisms through which contributes hepatocarcinogenesis remain poorly understood. extensive HCC patient cohorts identifies significant proportion copy number gains, are strongly linked adverse prognostic outcomes. By integrating RNA-Seq, ChIP-Seq, ATAC-seq, experimental validation, we show that overexpression activates mTORC1 signaling, subsequently promoting synthesis driving progression. We further uncover modulates epigenetic landscape by enhancing DNA methylation at ATF3 promoter, resulting repression subsequent activation mTORC1. This study elucidates novel regulatory axis links dysregulated progression, highlighting potential metabolic targets for therapeutic intervention.

Language: Английский

Glucagon-like Peptide-2 Acts Partially Through Central GLP-2R and MC4R in Mobilizing Stored Lipids from the Intestine DOI Open Access

Kundanika Mukherjee,

Muhammad Asaf Khan, John G. Howland

et al.

Nutrients, Journal Year: 2025, Volume and Issue: 17(9), P. 1416 - 1416

Published: April 23, 2025

Background: Glucagon-like peptide-2 (GLP-2) is a gut hormone secreted in response to nutrient intake and regulates lipid metabolism the gut. The present study aims elucidate underlying mechanism of GLP-2 stimulating secretion fasted state by testing whether signals through brain’s receptor melanocortin 4 (MC4R). Methods: Sprague-Dawley rats were implanted with mesenteric lymph duct cannula for measuring an intracerebroventricular infusion GLP-2R antagonist (GLP-2(11-33)), MC4R (SHU9119), or saline as control. rat received into small intestine peritoneal injection five hours later. Results: Brain administration attenuated stimulatory effects peripheral on triglyceride output. These associated differential changes expression key genes jejunal endothelial cells, smooth muscle neuronal cells. Conclusions: results support involvement central neural pathway mobilize lipids stored during post-absorptive state.

Language: Английский

Citations

0
Copy Number Gains of VPS72 Drive De Novo Lipogenesis and Hepatocarcinogenesis via ATF3/mTORC1/SREBP1 Axis DOI Creative Commons
Qinglin Zhang, Yunxing Huang, Yin Tong

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and a major contributor to cancer-related mortality globally. Central its pathogenesis dysregulation lipid metabolism in hepatocytes, leading abnormal accumulation. Our bioinformatics analysis has identified histone acetyltransferase complex subunit VPS72 as being associated with HCC, yet precise molecular mechanisms through which contributes hepatocarcinogenesis remain poorly understood. extensive HCC patient cohorts identifies significant proportion copy number gains, are strongly linked adverse prognostic outcomes. By integrating RNA-Seq, ChIP-Seq, ATAC-seq, experimental validation, we show that overexpression activates mTORC1 signaling, subsequently promoting synthesis driving progression. We further uncover modulates epigenetic landscape by enhancing DNA methylation at ATF3 promoter, resulting repression subsequent activation mTORC1. This study elucidates novel regulatory axis links dysregulated progression, highlighting potential metabolic targets for therapeutic intervention.

Language: Английский

Citations

0