Peroxisome proliferator-activated receptor α (PPARA) is a key mediator of lipid metabolism and inflammation. Activation of PPARA in rodents causes hepatocyte proliferation, but the underlying mechanism is poorly understood. This study focused on genes repressed by PPARA and analyzed the mechanism by which PPARA promotes hepatocyte proliferation in mice. Activation of PPARA by agonist treatment was autoregulated, and induced expression of the epigenetic regulator UHRF1 via activation of the newly described PPARA target gene , which, in turn, regulates . UHRF1 strongly repressed the expression of CDH1 via methylation of the promoter marked with H3K9me3. Repression of CDH1 by PPARA activation was reversed by PPARA deficiency or knockdown of E2F8 or UHRF1. Furthermore, a forced expression of CDH1 inhibited expression of the Wnt signaling target genes such as after PPARA activation, and suppressed hepatocyte hyperproliferation. These results demonstrate that the PPARA-E2F8-UHRF1-CDH1 axis causes epigenetic regulation of hepatocyte proliferation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036120 | PMC |
| http://dx.doi.org/10.1016/j.isci.2022.104196 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Regulatory role of lnc-MAP3K13-3:1 on miR-6894-3p and SHROOM2 in modulating cellular dynamics in hepatocellular carcinoma.
BMC Cancer
January 2025
Jiangxi Provincial Key Laboratory of Child Development and Genetics, Jiangxi Provincial Children's Hospital, No. 122 of YangMing Road, DongHu District, NanChang, 330006, China.
Background: Hepatocellular carcinoma (HCC) is a prevalent primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advancements in therapeutic strategies, the 5-year survival rate for individuals undergoing curative resection remains between 10% and 15%. Consequently, identifying molecular targets that specifically inhibit the proliferation and metastasis of HCC cells is critical for improving treatment outcomes.
View Article and Find Full Text PDFMechanical Analysis of Phellinus Linteus-Induced Apoptosis of Hepatoma Cells.
Microsc Res Tech
January 2025
International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun, China.
Liver cancer is prevalent with the third highest mortality rate globally. The biomechanical properties of cancer cells play a crucial role in their proliferation and differentiation. Studying the morphological and mechanical properties of individual living cells can be helpful for early diagnosis of cancers.
View Article and Find Full Text PDFSynergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma.
J Liver Cancer
January 2025
Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Background/aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1).
View Article and Find Full Text PDFA novel cobalt oxide nanoparticle conjugated with ellagic acid arrests the cell cycle in human liver cancer cell line.
Sci Rep
January 2025
Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.
The current chemotherapy treatments for liver cancer have shown limited effectiveness. Therefore, there is an urgent need to develop new drugs to combat this disease more effectively. This study reports synthesis of cobalt oxide nanoparticles coated with glucose, and conjugated with Ellagic acid.
View Article and Find Full Text PDFGossypol enhances ponatinib's cytotoxicity against human hepatocellular carcinoma cells by involving cell cycle arrest, p-AKT/LC3II/p62, and Bcl2/caspase-3 pathways.
Toxicol Rep
June 2025
Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza 12411, Egypt.
Despite significant breakthroughs in frontline cancer research and chemotherapy for hepatocellular carcinoma (HCC), many of the suggested drugs have high toxic side effects and resistance, limiting their clinical utility. Exploring potential therapeutic targets or novel combinations with fewer side effects is therefore crucial in combating this dreadful disease. The current study aims to use a novel combination of ponatinib and gossypol against the HepG2 cell line.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!