ArticleJournal of experimental & clinical cancer research : CR2020
BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 135 citations in OpenAlex.
- Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- O-GlcNAcylation Regulation of SNAP29-Dependent Autophagy Activation Dictates Chemoresistance in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- BMSC-derived exosomal METTL3 synergizes with Sevoflurane to inhibit ferroptosis in pulmonary ischemia/reperfusion injury by enhancing USP7 N6-methyladenosine modification.Apoptosis : an international journal on programmed cell death · 2026Article
- NRF2 deficiency impairs proliferation and survival of chicken primordial germ cells via oxidative stress, mitochondrial dysfunction and apoptosis.Poultry science · 2026Article
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- Altered Sphingolipid Metabolism is Associated with Osimertinib Resistance in Nonsmall-Cell Lung Cancer.Journal of proteome research · 2026Article
- Asporin promotes gastric cancer progression by regulating NRF2 ubiquitination and competitively binding to KEAP1.Translational cancer research · 2026Article
- Coenzyme Q10 exerts anti-cancer effects in bladder cancer by inducing ROS-mediated apoptosis and autophagy.Journal of bioenergetics and biomembranes · 2026Article
- Induction of TRIM22 promotes autophagy and apoptosis of colorectal cancer through reactive oxygen species generation.Journal of translational medicine · 2026Article
- Endothelial Cell Secretome Alterations Induced by Inflammatory Stress.bioRxiv : the preprint server for biology · 2026Article
- A Ubiquitination-Related Gene Prognostic Signature and the Oncogenic Role of RNF149 in Nasopharyngeal Carcinoma: scRNAseq- Based Bioinformatics and Experimental Validation.Current medicinal chemistry · 2026Article
- Bioinformatic Identification and Preliminary Validation of TP53, TGFB1, and NFE2L2 as Potential Ferroptosis-Related Regulators in Pancreatic Adenocarcinoma.Pharmacogenomics and personalized medicine · 2026Article
- Magnetically-Induced Suppression of Oxidative Stress Prevents Venous Thrombosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SLC25A39 identified as a key regulator of hepatocellular carcinoma progression through the mitochondrial ROS-cytochrome c-caspase signaling axis.Cellular & molecular biology letters · 2025Article
- PABPC1 Silencing Inhibits Gastric Cancer Cell Proliferation, Metastasis, and EMT Via the PI3K/AKT Pathway.Biochemical genetics · 2025Article
- SMAD3 orchestrates RNF167 and STAMBPL1-mediated Sestrin2 ubiquitination to drive gastric cancer progression.Cell division · 2025Article
- HNRNPH1 promotes autophagy to inhibit the development of lung adenocarcinoma via the HSP90AB1/MAP1LC3B axis.Respiratory research · 2025Article
- Identification of novel susceptibility loci for testicular germ cell tumors through multi-omics analysis.Discover oncology · 2025Article
- Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
background3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies.
methodsWestern blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays.
resultsBDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of Akt
conclusionsOur study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.
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