Evidence map›Paper›PMID 38488852›Full record

ArticleeLife2024

Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing associated with therapeutic response to splicing inhibitor.

Carolyn M Jablonowski, Waise Quarni, Shivendra Singh, Haiyan Tan, Dhanushka Hewa Bostanthirige, Hongjian Jin, Jie Fang, Ti-Cheng Chang, David Finkelstein, Ji-Hoon Cho and 11 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
8.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Versatile JMJD proteins: juggling histones and much more.Trends in biochemical sciences · 2024
    Review
  11. Article
  12. Review
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 3 institutions in 1 country.

Carolyn M Jablonowski *Department of Surgery, St Jude Children's Research Hospital, Memphis, United States.
Waise Quarni *Department of Surgery, St Jude Children's Research Hospital, Memphis, United States.
Shivendra SinghDepartment of Surgery, St Jude Children's Research Hospital, Memphis, United States.
Haiyan TanCenter for Proteomics and Metabolomics, St Jude Children's Research Hospital, Memphis, United States.
Dhanushka Hewa BostanthirigeDepartment of Surgery, St Jude Children's Research Hospital, Memphis, United States.
Hongjian JinCenter for Applied Bioinformatics, St Jude Children's Research Hospital, Memphis, United States.
Jie FangDepartment of Surgery, St Jude Children's Research Hospital, Memphis, United States.
Ti-Cheng ChangCenter for Applied Bioinformatics, St Jude Children's Research Hospital, Memphis, United States.
David FinkelsteinCenter for Applied Bioinformatics, St Jude Children's Research Hospital, Memphis, United States.
Ji-Hoon ChoCenter for Proteomics and Metabolomics, St Jude Children's Research Hospital, Memphis, United States.
Dongli HuDepartment of Surgery, St Jude Children's Research Hospital, Memphis, United States.
Vishwajeeth PagalaCenter for Proteomics and Metabolomics, St Jude Children's Research Hospital, Memphis, United States.
Sadie Miki SakuradaDepartment of Cell and Molecular Biology, St Jude Children's Research Hospital, Memphis, United States.
Shondra M Pruett-MillerDepartment of Cell and Molecular Biology, St Jude Children's Research Hospital, Memphis, United States.ORCID https://orcid.org/0000-0002-3793-585X
Ruoning WangCenter for Childhood Cancer and Blood Disease, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, United States.ORCID https://orcid.org/0000-0001-9798-8032
Andrew MurphyDepartment of Surgery, St Jude Children's Research Hospital, Memphis, United States.ORCID https://orcid.org/0000-0001-6747-0355
Kevin FreemanGenetics, Genomics & Informatics, The University of Tennessee Health Science Center (UTHSC), Memphis, United States.
Junmin PengDepartment of Structural Biology, St Jude Children's Research Hospital, Memphis, United States.
Andrew M DavidoffDepartment of Surgery, St Jude Children's Research Hospital, Memphis, United States.
Gang WuCenter for Applied Bioinformatics, St Jude Children's Research Hospital, Memphis, United States.
Jun YangDepartment of Surgery, St Jude Children's Research Hospital, Memphis, United States.ORCID https://orcid.org/0000-0002-4233-3220
St. Jude Children's Research Hospital · USNationwide Children's Hospital · USUniversity of Tennessee Health Science Center · US

Funding

Metabolic programming in TH17 cell differentiationR01AI114581 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI WANG, RUONING · 2015 to 2025
$3.6M
EXPLORE AND TARGET THE EPIGENETIC VULNERABILITY OF PAX3-FOXO1-DRIVEN RHABDOMYOSARCOMAR01CA266600 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Xiang Chen, Jun Yang · 2022 to 2026
$3.4M
Metabolic reprogramming of tumor microenvironment to maximize immunotherapy for pediatric cancersU01CA232488 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI WANG, RUONING · 2018 to 2018
$3.4M
Modulation of asparagine bioavailability and stress response signaling to enhance T cell robustness and maximize immunotherapyR01CA247941 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI WANG, RUONING · 2021 to 2025
$2.4M
Decipher and target GABA metabolism and GABA receptor-mediated signaling in autoimmune diseasesR01AI175004 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI Ruoning Wang · 2023 to 2026
$2.0M
Development of small molecules to target KDM4BR01CA229739 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHEN, TAOSHENG, DAVIDOFF, ANDREW M · 2018 to 2021
$1.6M
Oncogenic fusion gene FAX-FKHR in driving metabolic reprogramming in alveolar rhabdomyosarcomaR21CA227926 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI CHANDLER, DAWN S, WANG, RUONING · 2019 to 2020
$364k
The role of JMJD6 in MYC-mediated neuroblastomaR03CA212802 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI YANG, JUN · 2017 to 2018
$180k
NCI NIH HHS 1R01CA229739-01NCI NIH HHS R01 CA229739NCI NIH HHS R01 CA247941NCI NIH HHS R01 CA266600NCI NIH HHS R01CA266600NCI NIH HHS R03 CA212802NCI NIH HHS R21 CA227926NCI NIH HHS U01 CA232488NIAID NIH HHS R01 AI114581NIAID NIH HHS R01 AI175004
6 · The paper itself

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.

Indexed as

NeuroblastomaRNA PrecursorsSulfonamidesAnimalsGlutaminaseHumansJumonji Domain-Containing Histone DemethylasesMetabolic ReprogrammingMiceGlutaminaseJMJD6 protein, humanJumonji Domain-Containing Histone DemethylasesN-(3-chloro-7-indolyl)-1,4-benzenedisulphonamideRNA PrecursorsSulfonamidescancer biologyGLSindisulamJMJD6neuroblastomanonesplicing

Identifiers

PMID38488852
PMCPMC10942784
OpenAlexW4388125817

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.