ArticleOncogene2020
A novel KDM5A/MPC-1 signaling pathway promotes pancreatic cancer progression via redirecting mitochondrial pyruvate metabolism.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- Review
- MPC-mediated lactate production drives histone lactylation in dendritic cells to affect tumor progression and immunotherapy.Cellular and molecular life sciences : CMLS · 2025Article
- In silico development and validation of a novel six-gene-derived signature in hepatocellular carcinoma.Translational cancer research · 2025Article
- The KDM5A/HOXA5 axis regulates osteosarcoma progression via activating the Wnt/β-catenin pathway.European journal of medical research · 2025Article
- Current advances and future directions in targeting histone demethylases for cancer therapy.Molecules and cells · 2025Review
- Mitochondrial pyruvate dehydrogenase phosphatase metabolism disorder in malignant tumors.Oncology research · 2025Review
- KDM5D histone demethylase mediates p38α inactivation via its enzymatic activity to inhibit cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Unveiling therapeutic avenues targeting xCT in head and neck cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.Signal transduction and targeted therapy · 2024Review
- MARCH5 promotes aerobic glycolysis to facilitate ovarian cancer progression via ubiquitinating MPC1.Apoptosis : an international journal on programmed cell death · 2024Article
- Roles of Lysine Methylation in Glucose and Lipid Metabolism: Functions, Regulatory Mechanisms, and Therapeutic Implications.Biomolecules · 2024Review
- Identification of subgroups and development of prognostic risk models along the glycolysis-cholesterol synthesis axis in lung adenocarcinoma.Scientific reports · 2024Article
- Histone demethylase KDM5 regulates cardiomyocyte maturation by promoting fatty acid oxidation, oxidative phosphorylation, and myofibrillar organization.Cardiovascular research · 2024Article
- Hypoxia promotes metastasis by relieving miR-598-3p-restricted glycolysis in gastric cancer.Journal of translational medicine · 2024Article
- Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis.Cell death and differentiation · 2024Article
- The Molecular Twin artificial-intelligence platform integrates multi-omic data to predict outcomes for pancreatic adenocarcinoma patients.Nature cancer · 2024Article
- Domain architecture and protein-protein interactions regulate KDM5A recruitment to the chromatin.Epigenetics · 2023Review
- Novel Approaches to the Establishment of Local Microenvironment from Resorbable Biomaterials in the Brain In Vitro Models.International journal of molecular sciences · 2023Review
- Targeting Mitochondrial Metabolic Reprogramming as a Potential Approach for Cancer Therapy.International journal of molecular sciences · 2023Review
- Histone Modifications Represent a Key Epigenetic Feature of Epithelial-to-Mesenchyme Transition in Pancreatic Cancer.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitochondrial pyruvate carrier 1 (MPC-1) appears to be a tumor suppressor. In this study, we determined the regulation of MPC-1 expression by Lysine demethylase 5A (KDM5A) and critical impact of this novel KDM5A/MPC-1 signaling on PDA progression. TCGA database, paired PDA and adjacent normal pancreatic tissues, PDA tissue array and cell lines were used to determine the levels of MPC-1 and KDM5A expression, and their relationship with the clinicopathologic characteristics and overall survival (OS) of PDA patients. Both in vitro and in vivo models were used to determine biologic impacts of MPC-1 and KDM5A on PDA and mitochondrial pyruvate metabolism, and the mechanism underling reduced MPC-1 expression in PDA. The expression of MPC-1 was decreased in PDA cell lines and tissues, and negatively associated with tumor poorer differentiation, lymph nodes metastasis, higher TNM stages, and patients' overall survival (OS). Functional analysis revealed that restored expression of MPC-1 suppressed the growth, invasion, migration, stemness and tumorigenicity. Re-expression of MPC-1 stimulated the mitochondrial pyruvate metabolism and inhibited glycolysis, while MPC-1-specific inhibitor UK5099 attenuated these effects. Furthermore, KDM5A bound directly to MPC-1 promoter region and transcriptionally suppressed the expression of MPC-1 via demethylation H3K4. Consistently, KDM5A expression was elevated in PDA and promoted PDA cell proliferation in vitro and tumor growth in vivo via suppressing the expression of MPC-1. The expression of KDM5A was inversely correlated with that of MPC-1 in PDA. KDM5A/MPC-1 signaling promoted PDA growth, invasion, migration, and stemness via inhibiting mitochondrial pyruvate metabolism. Targeting KDM5A/MPC-1 signaling may be an effective therapeutic strategy for PDA.
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Registered trials
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.