Background And Aims: Our previous study showed that small-for-size liver graft may provide favorable micro-environment for tumor growth. GPx3, an anti-oxidant, not only attenuates oxidative stress, but also suppresses liver tumor growth in our recent study. Here, we aimed to characterize the clinical significance and explore the functional role of GPx3 in HCC recurrence after liver transplantation.
Methods: To explore the association between GPx3 expression and HCC invasiveness, a rat orthotopic liver transplantation model with tumor development was established. To investigate the clinical relevance of GPx3, 105 HCC patients who underwent liver transplantation were recruited. The suppressive role of GPx3 in HCC cells was studied using wound healing, Matrigel invasion assay and lung metastasis model. The real-time intravital imaging system was applied to directly visualize the tumor cells invasion in a living animal. The underlying mechanism was further explored.
Results: GPx3 was identified as a down-regulated protein in small-for-size liver graft and significantly associated with invasive phenotype of tumor growth in a rat model. Plasma GPx3 was significantly lower in small-for-size graft group post-transplantation (day1: 33 vs 1147; day3: 3209 vs 4459; day7: 303 vs 2506; mU/mL, P<0.05) in rat model. Clinically, the plasma GPx3 was significantly lower in the recipients with HCC recurrence post-transplantation (day1: 4.16 vs 8.99 µg/mL, P<0.001; day7: 3.86 vs 9.99 µg/mL, P<0.001). Furthermore, lower plasma GPx3 was identified as an independent predictor (HR=4.528, P=0.046) for poor overall survival post-transplantation. Over-expression of GPx3 significantly suppressed migration, invasiveness and metastasis of HCC cells. Real-time intravital imaging showed that GPx3 significantly suppressed HCC invasiveness in a live animal. GPx3 suppressed the tumor invasiveness through inhibition of JNK-cJun-MMP2 pathway.
Conclusion: GPx3 may possess prognostic and therapeutic value for HCC patients after liver transplantation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997247 | PMC |
| http://dx.doi.org/10.7150/thno.16023 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Candida albicans pathways that protect against organic peroxides and lipid peroxidation.
PLoS Genet
October 2024
Department of Microbiology and Immunology, Stony Brook University, Stony Brook, New York, United States of America.
Human fungal pathogens must survive diverse reactive oxygen species (ROS) produced by host immune cells that can oxidize a range of cellular molecules including proteins, lipids, and DNA. Formation of lipid radicals can be especially damaging, as it leads to a chain reaction of lipid peroxidation that causes widespread damage to the plasma membrane. Most previous studies on antioxidant pathways in fungal pathogens have been conducted with hydrogen peroxide, so the pathways used to combat organic peroxides and lipid peroxidation are not well understood.
View Article and Find Full Text PDFComparative Transcriptomes of Canine and Human Prostate Cancers Identify Mediators of Castration Resistance.
Vet Comp Oncol
December 2024
Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, Oregon, USA.
Prostate cancer continues to be one of the most lethal cancers in men. While androgen deprivation therapy is initially effective in treating prostate cancer, most cases of advanced prostate cancer eventually progress to castration-resistant prostate cancer (CRPC), which is incurable. Similarly, the most aggressive form of prostatic carcinoma occurs in dogs that have been castrated.
View Article and Find Full Text PDFSelenium deficiency modulates necroptosis-mediated intestinal inflammation in broiler through the lncRNAWSF27/miRNA1696/GPX3 axis.
J Anim Sci
September 2024
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
Article Synopsis
- Selenium deficiency in broilers leads to severe health issues, including diarrhea and increased mortality, while current solutions don’t effectively tackle intestinal inflammation.
- Researchers replicated a selenium-deficient condition and found that it caused oxidative stress and inflammation in the intestines by lowering the expression of glutathione peroxidase (GPX) 3.
- The study investigated the lncRNAWSF27/miR-1696/GPX3 regulatory axis, highlighting its role in mediating intestinal inflammation caused by selenium deficiency and indicating potential therapeutic strategies for improving broiler health.
Glutathione peroxidase 3 is essential for countering senescence in adipose remodelling by maintaining mitochondrial homeostasis.
Redox Biol
November 2024
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, China; Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:
Adipose tissue senescence is a precursor to organismal aging and understanding adipose remodelling contributes to discovering novel anti-aging targets. Glutathione peroxidase 3 (GPx3), a critical endogenous antioxidant enzyme, is diminished in the subcutaneous adipose tissue (sWAT) with white adipose expansion. Based on the active role of the antioxidant system in counteracting aging, we investigated the involvement of GPx3 in adipose senescence.
View Article and Find Full Text PDFThe Dynamics of Methylation Concentrations in Glutathione Peroxidase 3 Promoter from Patients with Chronic Heart Failure and Their Association with Key Clinical Parameters.
J Nutr
November 2024
School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, China. Electronic address:
Objective: This study investigated changes in methylation concentrations within the glutathione peroxidase 3 (GPX3) promoter region among patients diagnosed with chronic heart failure (CHF). Peripheral blood samples were collected from 20 CHF patients and 20 healthy individuals for analysis.
Methods: Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, methylation concentrations of 11 CpG sites within the GPX3 promoter region were quantified.
Want 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!