Evidence map›Paper›PMID 30933831›Full record

ArticleMolecular therapy. Nucleic acids2019

Exploring the MIR143-UPAR Axis for the Inhibition of Human Prostate Cancer Cells In Vitro and In Vivo.

Sven Wach, Madeleine Brandl, Hannes Borchardt, Katrin Weigelt, Sabine Lukat, Elke Nolte, Omar Al-Janabi, Martin Hart, Friedrich Grässer, Johannes Giedl and 10 more

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 21% 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

19 citing papers in PubMed, 29 citations in OpenAlex.

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  16. Non-coding RNAs and potential therapeutic targeting in cancer.Biochimica et biophysica acta. Reviews on cancer · 2021
    Review
  17. Oncogenic and tumor-suppressive microRNAs in prostate cancer.Current opinion in endocrine and metabolic research · 2020
    Article
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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

20 authors at 4 institutions in 1 country.

Sven WachDepartment of Urology, Friedrich Alexander University Hospital Erlangen-Nürnberg, Erlangen, Germany.
Madeleine BrandlRudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Leipzig, Germany.
Hannes BorchardtRudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Leipzig, Germany.
Katrin WeigeltDepartment of Urology, Friedrich Alexander University Hospital Erlangen-Nürnberg, Erlangen, Germany.
Sabine LukatDepartment of Urology, Friedrich Alexander University Hospital Erlangen-Nürnberg, Erlangen, Germany.
Elke NolteDepartment of Urology, Friedrich Alexander University Hospital Erlangen-Nürnberg, Erlangen, Germany.
Omar Al-JanabiDepartment of Urology, Friedrich Alexander University Hospital Erlangen-Nürnberg, Erlangen, Germany.
Martin HartInstitute of Virology, University of Saarland Medical School, Kirrbergerstrasse, Homburg/Saar, Germany.
Friedrich GrässerInstitute of Virology, University of Saarland Medical School, Kirrbergerstrasse, Homburg/Saar, Germany.
Johannes GiedlInstitute of Pathology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Rudolf JungInstitute of Pathology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Robert StöhrInstitute of Pathology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Arndt HartmannInstitute of Pathology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Verena LiebDepartment of Urology, Friedrich Alexander University Hospital Erlangen-Nürnberg, Erlangen, Germany.
Sabrina HöbelRudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Leipzig, Germany.
Anna PetersRudolf-Schönheimer-Institute for Biochemistry, University of Leipzig, Leipzig, Germany.
Claudia StäubertRudolf-Schönheimer-Institute for Biochemistry, University of Leipzig, Leipzig, Germany.
Bernd WullichDepartment of Urology, Friedrich Alexander University Hospital Erlangen-Nürnberg, Erlangen, Germany.
Helge TaubertDepartment of Urology, Friedrich Alexander University Hospital Erlangen-Nürnberg, Erlangen, Germany. Electronic address: helge.taubert@uk-erlangen.de.
Achim AignerRudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Leipzig, Germany.
Friedrich-Alexander-Universität Erlangen-Nürnberg · DELeipzig University · DESaarland University · DEUniversitätsklinikum Erlangen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MIR143 is pathologically downregulated and may function as a tumor suppressor in prostate cancer. Likewise, the urokinase plasminogen activator receptor (UPAR) is overexpressed in prostate carcinoma, representing a negative prognostic marker and putative therapeutic target gene. In this paper, we establish UPAR as a new direct target of MIR143. Luciferase reporter gene constructs identify one of the two in silico-predicted binding sites as functionally relevant for direct MIR143 binding to the 3' UTR, and, concomitantly, transfection of MIR143 reduces UPAR protein levels in prostate carcinoma cells in vitro. Inhibitory effects on cell proliferation and colony formation, spheroid growth and integrity, and cell viability are extensively analyzed, and they are compared to direct small interfering RNA (siRNA)-mediated uPAR knockdown or combined microRNA (miRNA)-siRNA treatment. Switching to a therapeutically more relevant in vivo model, we demonstrate tumor-inhibitory effects of MIR143 replacement therapy by systemic treatment of mice bearing subcutaneous PC-3 tumor xenografts with MIR143 formulated in polymeric nanoparticles. This efficient, nanoparticle-mediated delivery of intact MIR143 mediates the marked downregulation of uPAR protein, but not mRNA levels, thus indicating translational inhibition rather than mRNA degradation. In summary, we identify UPAR as a direct target gene of MIR143, and we establish the therapeutic anti-tumor potential of nanoparticle-based MIR143 replacement in prostate cancer.

Indexed as

MIR143miRNA replacementPEI nanoparticlesprostate cancerurokinase plasminogen activator receptorxenograft

Identifiers

PMID30933831
PMCPMC6444223
OpenAlexW2915267181

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.