ArticleeLife2024
Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing associated with therapeutic response to splicing inhibitor.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 34 citations in OpenAlex.
- Dysregulation of SCARB1 Alternative Splicing Disturbs Amino Acid Metabolism in Anembryonic Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Histone arginine demethylase JMJD7 promotes bone formation through regulating α-Ketoglutarate metabolism.Cell death and differentiation · 2026Article
- Pan-cancer analysis identifies JMJD6 as an oncogene and prognostic biomarker.Discover oncology · 2026Article
- BCLAF1 links RNA splicing to ATF4-dependent metabolic adaptation in acute myeloid leukemia.bioRxiv : the preprint server for biology · 2026Article
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
- RBM39 Promotes Base Excision Repair to Facilitate the Progression of HCC by Stabilising OGG1 mRNA.Cell proliferation · 2025Article
- Conditional Activation of c-MYC in Distinct Catecholaminergic Cells Drives Development of Neuroblastoma or Somatostatinoma.Cancer research · 2025Article
- Jumonji domain-containing protein 6 promotes gastric cancer progression: Modulating immune evasion through autophagy and oxidative stress pathways.CytoJournal · 2025Article
- Versatile JMJD proteins: juggling histones and much more.Trends in biochemical sciences · 2024Review
- Targeting RBM39 through indisulam induced mis-splicing of mRNA to exert anti-cancer effects in T-cell acute lymphoblastic leukemia.Journal of experimental & clinical cancer research : CR · 2024Article
- To Erase or Not to Erase: Non-Canonical Catalytic Functions and Non-Catalytic Functions of Members of Histone Lysine Demethylase Families.International journal of molecular sciences · 2024Review
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21 authors at 3 institutions in 1 country.
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Abstract
Dysregulated pre-mRNA splicing and metabolism are two hallmarks of MYC-driven cancers. Pharmacological inhibition of both processes has been extensively investigated as potential therapeutic avenues in preclinical and clinical studies. However, how pre-mRNA splicing and metabolism are orchestrated in response to oncogenic stress and therapies is poorly understood. Here, we demonstrate that jumonji domain containing 6, arginine demethylase, and lysine hydroxylase, JMJD6, acts as a hub connecting splicing and metabolism in MYC-driven human neuroblastoma. JMJD6 cooperates with MYC in cellular transformation of murine neural crest cells by physically interacting with RNA binding proteins involved in pre-mRNA splicing and protein homeostasis. Notably, JMJD6 controls the alternative splicing of two isoforms of glutaminase (GLS), namely kidney-type glutaminase (KGA) and glutaminase C (GAC), which are rate-limiting enzymes of glutaminolysis in the central carbon metabolism in neuroblastoma. Further, we show that JMJD6 is correlated with the anti-cancer activity of indisulam, a 'molecular glue' that degrades splicing factor RBM39, which complexes with JMJD6. The indisulam-mediated cancer cell killing is at least partly dependent on the glutamine-related metabolic pathway mediated by JMJD6. Our findings reveal a cancer-promoting metabolic program is associated with alternative pre-mRNA splicing through JMJD6, providing a rationale to target JMJD6 as a therapeutic avenue for treating MYC-driven cancers.
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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.