ArticleJournal of experimental & clinical cancer research : CR2021
A HIF1α-GPD1 feedforward loop inhibits the progression of renal clear cell carcinoma via mitochondrial function and lipid metabolism.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 53 citations in OpenAlex.
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- Pharmacological induction of acetyl-CoA carboxylase 1 autophagic degradation attenuates lipid accumulation and cholangiocarcinoma progression.Journal of experimental & clinical cancer research : CR · 2025Article
- Lipid reprogramming and ferroptosis crosstalk in clear cell renal cell carcinoma: metabolic vulnerabilities and therapeutic targeting.Molecular cancer · 2025Review
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- Integrated multi-sample transcriptomic analysis of COVID-19 patients against controls using a bioinformatics pipeline.Scientific reports · 2025Article
- The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma.Cell death discovery · 2025Review
- Glycogen metabolism genes as a molecular signature for subtyping, prognostic prediction, and immunotherapy selection in clear cell renal cell carcinoma.Clinical and experimental medicine · 2025Article
- Identification and Validation of Lipid Metabolism-Related Biomarkers GPD1 and CEBPD in Metabolic Dysfunction-Associated Steatohepatitis.Journal of inflammation research · 2025Article
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- Intraovarian injection of 3D-MSC-EVs-ECM gel significantly improved rat ovarian function after chemotherapy.Reproductive biology and endocrinology : RB&E · 2024Article
- Lipid metabolism reprogramming in renal cell carcinomas.Medical oncology (Northwood, London, England) · 2024Review
- Comprehensive Analysis of a Six-Gene Signature Predicting Survival and Immune Infiltration of Liposarcoma Patients and Deciphering Its Therapeutic Significance.International journal of molecular sciences · 2024Article
- Identification of potential modulators for human GPD1 by docking-based virtual screening, molecular dynamics simulations, binding free energy calculations, and DeLA-drug analysis.Scientific reports · 2024Article
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundHypoxia signaling, especially the hypoxia inducible factor (HIF) pathway, is a major player in clear cell renal cell carcinoma (ccRCC), which is characterized by disorders in lipid and glycogen metabolism. However, the interaction between hypoxia and lipid metabolism in ccRCC progression is still poorly understood.
methodsWe used bioinformatic analysis and discovered that glycerol-3-phosphate dehydrogenase 1 (GPD1) may play a key role in hypoxia and lipid metabolism pathways in ccRCC. Tissue microarray, IHC staining, and survival analysis were performed to evaluate clinical function. In vitro and in vivo assays showed the biological effects of GPD1 in ccRCC progression.
resultsWe found that the expression of GPD1 was downregulated in ccRCC tissues, and overexpression of GPD1 inhibited the progression of ccRCC both in vivo and in vitro. Furthermore, we demonstrated that hypoxia inducible factor-1α (HIF1α) directly regulates GPD1 at the transcriptional level, which leads to the inhibition of mitochondrial function and lipid metabolism. Additionally, GPD1 was shown to inhibit prolyl hydroxylase 3 (PHD3), which blocks prolyl-hydroxylation of HIF1α and subsequent proteasomal degradation, and thus reinforces the inhibition of mitochondrial function and phosphorylation of AMPK via suppressing glycerol-3-phosphate dehydrogenase 2 (GPD2).
conclusionsThis study not only demonstrated that HIF1α-GPD1 forms a positive feedforward loop inhibiting mitochondrial function and lipid metabolism in ccRCC, but also discovered a new mechanism for the molecular basis of HIF1α to inhibit tumor activity, thus providing novel insights into hypoxia-lipid-mediated ccRCC therapy.
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