Evidence map›Paper›PMID 32464274›Full record

ArticleNeoplasia (New York, N.Y.)2020

Molecular mechanisms of Guadecitabine induced FGFR4 down regulation in alveolar rhabdomyosarcomas.

Emad Darvishi, Katherine Slemmons, Zesheng Wan, Sheetal Mitra, Xiaogang Hou, Jean Hugues Parmentier, Yong-Hwee Eddie Loh, Lee J Helman

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 40% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  3. Super-enhancers complexes zoom in transcription in cancer.Journal of experimental & clinical cancer research : CR · 2023
    Review
  4. Review
  5. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Emad DarvishiDivision of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Katherine SlemmonsDivision of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Zesheng WanDivision of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Sheetal MitraDivision of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Xiaogang HouDivision of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Jean Hugues ParmentierDivision of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Yong-Hwee Eddie LohUSC Libraries Bioinformatics Services, Los Angeles, CA, USA.
Lee J HelmanDivision of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: lhelman@chla.usc.edu.
Children's Hospital of Los Angeles · USAssociation of Research Libraries · USUniversity of Southern California · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fibroblast growth factor receptor 4 (FGFR4) aberrant expression and activity have been linked to the pathogenesis of a variety of cancers including rhabdomyosarcomas (RMS). We found that treatment of alveolar rhabdomyosarcoma (aRMS) cells with Guadecitabine (SGI-110), a next-generation DNA methyltransferase inhibitor (DNMTi), resulted in a significant reduction of FGFR4 protein levels, 5 days post treatment. Chromatin immunoprecipitation-sequencing (ChIP-seq) in aRMS cells revealed attenuation of the H3K4 mono-methylation across the FGFR4 super enhancer without changes in tri-methylation of either H3K4 or H3K27. These changes were associated with a significant reduction in FGFR4 transcript levels in treated cells. These decreases in H3K4me1 in the FGFR4 super enhancer were also associated with a 240-fold increase in KDM5B (JARID1B) mRNA levels. Immunoblot and immunofluorescent studies also revealed a significant increase in the KDM5B protein levels after treatment in these cells. KDM5B is the only member of KDM5 (JARID1) family of histone lysine demethylases that catalyzes demethylation of H3K4me1. These data together suggest a pleiotropic effect of DNMTi therapy in aRMS cells, converging to significantly lower FGFR4 protein levels in these cells.

Indexed as

Antineoplastic AgentsAzacitidineCell Line, TumorCell ProliferationChromatin Immunoprecipitation SequencingDown-RegulationEnhancer Elements, GeneticHistonesHumansJumonji Domain-Containing Histone DemethylasesLysineNuclear ProteinsReceptor, Fibroblast Growth Factor, Type 4Repressor ProteinsRhabdomyosarcoma, AlveolarAntineoplastic AgentsAzacitidineFGFR4 protein, humanguadecitabineHistonesJumonji Domain-Containing Histone DemethylasesKDM5B protein, humanLysineNuclear ProteinsReceptor, Fibroblast Growth Factor, Type 4Repressor ProteinsAlveolar rhabdomyosarcoma (aRMS)Epigenetic marksFibroblast growth factor receptor 4 (FGFR4)Guadecitabine (SGI-110)Histone lysine demethylase 5B (KDM5B)

Identifiers

PMID32464274
PMCPMC7251315
OpenAlexW3032864336

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.