ArticleRedox biology2024
Inhibition of KDM4A restricts SQLE transcription and induces oxidative stress imbalance to suppress bladder cancer.
Article in Redox biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed.
- KDM4A drives TGCT metastasis by inducing focal adhesion disassembly via STAT1-mediated CCL3 transcriptional activation.Oncogene · 2026Article
- Squalene attenuates doxorubicin resistance in hepatocellular carcinoma by targeting SIRT6 to inhibit ERK1 deacetylation.Molecular and cellular biochemistry · 2026Article
- SQLE as a potential diagnostic and prognostic biomarker for LIHC: a multi-cohort and spatial study.NPJ precision oncology · 2026Article
- Knockout of kdm4aa inhibits early embryonic development in zebrafish via downregulating cyp26a1.Molecular genetics and genomics : MGG · 2026Article
- Post-translational modifications: Principal regulators of bladder cancer.Molecular biology reports · 2026Review
- Harnessing PDX and PDX 2.0: the next-generation paradigm for precision oncology and translational breakthroughs.Molecular cancer · 2026Review
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Histone demethylase KDM4A promotes endometrial cancer progression through an ERRγ-associated cell-cycle regulatory axis.International journal of biological sciences · 2026Article
- USP7 promotes chemotherapy resistance and DNA damage response through stabilizing and deubiquitinating KDM4A in bladder cancer.Cell death & disease · 2025Article
- SQLE drives bladder cancer progression by boosting mitochondrial oxidative phosphorylation.Oncogene · 2025Article
- Circ_0003266 suppresses bladder cancer progression by modulating the miR-503-5p/SMAD7/TGF-β signaling axis.Scientific reports · 2025Article
- Identification and validation of SQLE in steroid-induced osteonecrosis of the femoral head: a bioinformatics and experimental study.Journal of orthopaedic surgery and research · 2025Article
- Review
- DNA Methylation in Bladder Cancer: Diagnostic and Therapeutic Perspectives-A Narrative Review.International journal of molecular sciences · 2025Review
- Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ferroptosis: iron release mechanisms in the bioenergetic process.Cancer metastasis reviews · 2025Review
- Zinc sulfate improves insulin resistance, oxidative stress and apoptosis in liver tissues of PCOS rats through the NF-κB pathway.Frontiers in endocrinology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In clinical practice, the limited efficacy of standard comprehensive therapy for advanced bladder cancer and the lack of targeted treatment options are well recognized. Targeting abnormal epigenetic modifications in tumors has shown considerable potential in cancer therapy. Through drug screening in tumor organoids, we identified that ML324, a histone lysine demethylase 4A (KDM4A) inhibitor, exhibits potent antitumor effects in both in vitro and in vivo cancer models. Mechanistically, Kdm4a demethylates H3K9me3, leading to chromatin opening and increased accessibility of Gabpa to the squalene epoxidase (Sqle) gene promoter, resulting in transcriptional activation. Inhibition of Kdm4a downregulates Sqle transcription, blocking cholesterol synthesis and causing squalene (SQA) accumulation. This process induces reactive oxygen species (ROS) clearance and suppresses JNK/c-Jun phosphorylation, ultimately inducing apoptosis. Furthermore, ML324 treatment significantly inhibited tumor growth in bladder cancer patient-derived xenograft (PDX) models. Our findings reveal the presence of a Kdm4a-Sqle-ROS-JNK/c-Jun signaling axis that regulates oxidative stress balance, offering a novel strategy for targeted therapy in bladder cancer.
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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.