ArticlePloS one2016
Inhibition of Prostaglandin Reductase 2, a Putative Oncogene Overexpressed in Human Pancreatic Adenocarcinoma, Induces Oxidative Stress-Mediated Cell Death Involving xCT and CTH Gene Expressions through 15-Keto-PGE2.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Heritable pulmonary arterial hypertension: new genetic findings and environmental triggers.Scientific reports · 2026Article
- Genome-wide CRISPR/Cas9 screening identifies PTGR2 as a potential therapeutic target for sunitinib resistance in clear cell renal cell carcinoma.Scientific reports · 2025Article
- Human PTGR2 Inactivation Alters Eicosanoid Metabolism and Cytokine Response of Inflammatory Macrophages.ACS chemical biology · 2025Article
- Glycolysis-Driven Prognostic Model for Acute Myeloid Leukemia: Insights into the Immune Landscape and Drug Sensitivity.Biomedicines · 2025Article
- Unbiased Single-Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data.Frontiers in physiology · 2023Article
- Tissue lipidomic profiling supports a mechanistic role of the prostaglandin E2 pathway for albuminuria development in glomerular hyperfiltration.Frontiers in network physiology · 2023Article
- Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2.Chembiochem : a European journal of chemical biology · 2021Article
- Investigation of monogenic causes of familial breast cancer: data from the BEACCON case-control study.NPJ breast cancer · 2021Article
- Emerging roles of the solute carrier family in pancreatic cancer.Clinical and translational medicine · 2021Review
- 15-Keto prostaglandin ERedox biology · 2019Article
- Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas.Scientific reports · 2019Article
- Research Advances in the Correlation between Peroxisome Proliferator-Activated Receptor-PPAR research · 2018Review
- Solute carrier transporters: potential targets for digestive system neoplasms.Cancer management and research · 2018Review
- Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics.ACS chemical biology · 2017Article
- Alkaline Phosphatase-To-Albumin Ratio as a Prognostic Indicator in Pancreatic Ductal Adenocarcinoma after Curative Resection.Journal of Cancer · 2017Article
- Association of single nucleotide polymorphism rs2065955 of the filaggrin gene with susceptibility to Epstein-Barr virus-associated gastric carcinoma and EBV-negative gastric carcinoma.Virologica Sinica · 2016Article
- High Expression of PTGR1 Promotes NSCLC Cell Growth via Positive Regulation of Cyclin-Dependent Protein Kinase Complex.BioMed research international · 2016Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostaglandin reductase 2 (PTGR2) is the enzyme that catalyzes 15-keto-PGE2, an endogenous PPARγ ligand, into 13,14-dihydro-15-keto-PGE2. Previously, we have reported a novel oncogenic role of PTGR2 in gastric cancer, where PTGR2 was discovered to modulate ROS-mediated cell death and tumor transformation. In the present study, we demonstrated the oncogenic potency of PTGR2 in pancreatic cancer. First, we observed that the majority of the human pancreatic ductal adenocarcinoma tissues was stained positive for PTGR2 expression but not in the adjacent normal parts. In vitro analyses showed that silencing of PTGR2 expression enhanced ROS production, suppressed pancreatic cell proliferation, and promoted cell death through increasing 15-keto-PGE2. Mechanistically, silencing of PTGR2 or addition of 15-keto-PGE2 suppressed the expressions of solute carrier family 7 member 11 (xCT) and cystathionine gamma-lyase (CTH), two important providers of intracellular cysteine for the generation of glutathione (GSH), which is widely accepted as the first-line antioxidative defense. The oxidative stress-mediated cell death after silencing of PTGR2 or addition of 15-keto-PGE2 was further abolished after restoring intracellular GSH concentrations and cysteine supply by N-acetyl-L-cysteine and 2-Mercaptomethanol. Our data highlight the therapeutic potential of targeting PTGR2/15-keto-PGE2 for pancreatic cancer.
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