Evidence map›Paper›PMID 25886616›Full record

ArticleJournal of hematology & oncology2015

EVI1 promotes tumor growth via transcriptional repression of MS4A3.

Gerwin Heller, Anna Rommer, Katarina Steinleitner, Julia Etzler, Hubert Hackl, Petra Heffeter, Erwin Tomasich, Martin Filipits, Birgit Steinmetz, Thais Topakian and 6 more

Open access · goldAbstract read
In one paragraph

Article in Journal of hematology & oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

25 citing papers in PubMed, 33 citations in OpenAlex.

  1. Trial
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  3. Journal of gastrointestinal oncology · 2026
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  14. Review
  15. EVI1 as a Marker for Lymph Node Metastasis in HNSCC.International journal of molecular sciences · 2020
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. The role of zinc and its compounds in leukemia.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018
    Review
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

16 authors at 3 institutions in 1 country.

Gerwin HellerDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. gerwin.heller@meduniwien.ac.at.
Anna RommerDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. apm.rommer@gmail.com.
Katarina SteinleitnerDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. katarina.steinleitner@meduniwien.ac.at.
Julia EtzlerDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. julia.etzler@meduniwien.ac.at.
Hubert HacklBiocenter, Division of Bioinformatics, Medical University of Innsbruck, Innrain 80, 6020, Innsbruck, Austria. hubert.hackl@i-med.ac.at.
Petra HeffeterComprehensive Cancer Center of the Medical University of Vienna, Vienna, Austria. petra.heffeter@meduniwien.ac.at.
Erwin TomasichDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. erwin.tomasich@meduniwien.ac.at.
Martin FilipitsComprehensive Cancer Center of the Medical University of Vienna, Vienna, Austria. martin.filipits@meduniwien.ac.at.
Birgit SteinmetzDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. birgit.steinmetz@meduniwien.ac.at.
Thais TopakianDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. thais.topakian@meduniwien.ac.at.
Simone KlingenbrunnerDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. sim.kling@gmx.at.
Barbara ZieglerDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. barbara.ziegler@meduniwien.ac.at.
Andreas SpittlerCore Facility Flow Cytometry & Surgical Research Laboratories, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. andreas.spittler@meduniwien.ac.at.
Sabine Zöchbauer-MüllerDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. sabine.zoechbauer-mueller@meduniwien.ac.at.
Walter BergerComprehensive Cancer Center of the Medical University of Vienna, Vienna, Austria. walter.berger@meduniwien.ac.at.
Rotraud WieserDepartment of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. rotraud.wieser@meduniwien.ac.at.
Medical University of Vienna · ATComprehensive Cancer Center Vienna · ATUniversität Innsbruck · AT

Funding

Austrian Science Fund FWF P 20920Austrian Science Fund FWF P 21401Austrian Science Fund FWF P 24130
6 · The paper itself

Abstract

backgroundThe transcription factor Ecotropic Virus Integration site 1 (EVI1) regulates cellular proliferation, differentiation, and apoptosis, and its overexpression contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells.

methodsU937T_EVI1, a human myeloid cell line expressing EVI1 in a tetracycline regulable manner, was subjected to gene expression profiling. qRT-PCR was used to confirm the regulation of membrane-spanning-4-domains subfamily-A member-3 (MS4A3) by EVI1. Reporter constructs containing various parts of the MS4A3 upstream region were employed in luciferase assays, and binding of EVI1 to the MS4A3 promoter was investigated by chromatin immunoprecipitation. U937 derivative cell lines experimentally expressing EVI1 and/or MS4A3 were generated by retroviral transduction, and tested for their tumorigenicity by subcutaneous injection into severe combined immunodeficient mice.

resultsGene expression microarray analysis identified 27 unique genes that were up-regulated, and 29 unique genes that were down-regulated, in response to EVI1 induction in the human myeloid cell line U937T. The most strongly repressed gene was MS4A3, and its down-regulation by EVI1 was confirmed by qRT-PCR in additional, independent experimental model systems. MS4A3 mRNA levels were also negatively correlated with those of EVI1 in several published AML data sets. Reporter gene assays and chromatin immunoprecipitation showed that EVI1 regulated MS4A3 via direct binding to a promoter proximal region. Experimental re-expression of MS4A3 in an EVI1 overexpressing cell line counteracted the tumor promoting effect of EVI1 in a murine xenograft model by increasing the rate of apoptosis.

conclusionsOur data reveal MS4A3 as a novel direct target of EVI1 in human myeloid cells, and show that its repression plays a role in EVI1 mediated tumor aggressiveness.

Indexed as

Cell ProliferationTranscription, GeneticAnimalsCell Cycle ProteinsCell Line, TumorChromatin ImmunoprecipitationDNA-Binding ProteinsFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticGene Knockdown TechniquesHeterograftsHumansImmunohistochemistryLeukemia, MyeloidMaleMDS1 and EVI1 Complex Locus ProteinCell Cycle ProteinsDNA-Binding ProteinsMDS1 and EVI1 Complex Locus ProteinMECOM protein, humanMembrane ProteinsMS4A3 protein, humanTranscription Factors

Identifiers

PMID25886616
PMCPMC4389965
OpenAlexW2129984982

What OpenQuestion holds

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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.