Evidence map›Paper›PMID 25401475›Full record

ArticleThe Journal of clinical investigation2014

Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis.

Michelle Marques Howarth, David Simpson, Siu P Ngok, Bethsaida Nieves, Ron Chen, Zurab Siprashvili, Dedeepya Vaka, Marcus R Breese, Brian D Crompton, Gabriela Alexe and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Unlocking epigenetics for precision treatment of Ewing's sarcoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024
    Article
  8. Circulating long non-coding RNANon-coding RNA research · 2024
    Article
  9. Article
  10. Review
  11. Review
  12. EWS::FLI1 and HOXD13 Control Tumor Cell Plasticity in Ewing Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. International journal of molecular sciences · 2021
    Article
  18. Review
  19. Review
  20. Article
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

18 authors at 7 institutions in 2 countries.

Michelle Marques Howarth
David Simpson
Siu P Ngok
Bethsaida Nieves
Ron Chen
Zurab Siprashvili
Dedeepya Vaka
Marcus R Breese
Brian D Crompton
Gabriela Alexe
Doug S Hawkins
Damon Jacobson
Alayne L Brunner
Robert West
Jaume Mora
Kimberly Stegmaier
Paul Khavari
E Alejandro Sweet-Cordero
Stanford University · USDana-Farber Cancer Institute · USBoston Children's Hospital · USCancer Research Center · USHospital Sant Joan de Déu Barcelona · ESUniversity of Washington · USVA Palo Alto Health Care System · US

Funding

Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
NCI NIH HHS T32 CA009302NCI NIH HHS T32CA009302
6 · The paper itself

Abstract

Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma. EWS-FLI1 alters gene expression through mechanisms that are not completely understood. We performed RNA sequencing (RNAseq) analysis on primary pediatric human mesenchymal progenitor cells (pMPCs) expressing EWS-FLI1 in order to identify gene targets of this oncoprotein. We determined that long noncoding RNA-277 (Ewing sarcoma-associated transcript 1 [EWSAT1]) is upregulated by EWS-FLI1 in pMPCs. Inhibition of EWSAT1 expression diminished the ability of Ewing sarcoma cell lines to proliferate and form colonies in soft agar, whereas EWSAT1 inhibition had no effect on other cell types tested. Expression of EWS-FLI1 and EWSAT1 repressed gene expression, and a substantial fraction of targets that were repressed by EWS-FLI1 were also repressed by EWSAT1. Analysis of RNAseq data from primary human Ewing sarcoma further supported a role for EWSAT1 in mediating gene repression. We identified heterogeneous nuclear ribonucleoprotein (HNRNPK) as an RNA-binding protein that interacts with EWSAT1 and found a marked overlap in HNRNPK-repressed genes and those repressed by EWS-FLI1 and EWSAT1, suggesting that HNRNPK participates in EWSAT1-mediated gene repression. Together, our data reveal that EWSAT1 is a downstream target of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes.

Indexed as

Gene Expression Regulation, NeoplasticCell Line, TumorCell Transformation, NeoplasticDown-RegulationHeterogeneous-Nuclear Ribonucleoprotein KHumansOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RibonucleoproteinsRNA-Binding Protein EWSRNA, Long NoncodingRNA, NeoplasmSarcoma, EwingSequence Analysis, RNAUp-RegulationEWS-FLI fusion proteinHeterogeneous-Nuclear Ribonucleoprotein KHNRNPK protein, humanOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RibonucleoproteinsRNA-Binding Protein EWSRNA, Long NoncodingRNA, Neoplasm

Identifiers

PMID25401475
PMCPMC4348951
OpenAlexW1988957007

What OpenQuestion holds

Textmetadata
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.