Evidence map›Paper›PMID 19671150›Full record

ArticleMolecular cancer2009

Antisense gapmers selectively suppress individual oncogenic p73 splice isoforms and inhibit tumor growth in vivo.

Stephan Emmrich, Weiwei Wang, Katja John, Wenzhong Li, Brigitte M Pützer

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.2field-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

23 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Review
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  5. Mechanisms of Functional Pleiotropy of p73 in Cancer and Beyond.Frontiers in cell and developmental biology · 2021
    Review
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  9. Overexpression of the ∆Np73 isoform is associated with centrosome amplification in brain tumor cell lines.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
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  18. Advancement and prospects of tumor gene therapy.Chinese journal of cancer · 2011
    Review
  19. p73 as a pharmaceutical target for cancer therapy.Current pharmaceutical design · 2011
    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

5 authors at 1 institution in 1 country.

Stephan EmmrichDepartment of Vectorology and Experimental Gene Therapy, Biomedical Research Center, University of Rostock, D-18057 Rostock, Germany. emmrichs@med.uni-rostock.de
Weiwei Wang
Katja John
Wenzhong Li
Brigitte M Pützer
University of Rostock · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDifferential mRNA splicing and alternative promoter usage of the TP73 gene results in the expression of multiple NH2-truncated isoforms that act as oncogenes. Abundant levels of these p73 variants in a variety of human cancers correlated with adverse clinical prognosis and response failure to conventional therapies, underscoring their relevance as marker for disease severity and target for cancer intervention. With respect to an equally important role for amino-truncated p73 splice forms (DeltaTAp73) and DeltaNp73 (summarized as DNp73) in the tumorigenic process, we designed locked nucleic acid (LNA) antisense oligonucleotide (ASO) gapmers against individual species that were complementary to DeltaEx2 and DeltaEx2/3 splice junctions and a region in exon 3B unique for DeltaN' and DeltaN.

resultsTreatment of cancer cells with these ASOs resulted in a strong and specific reduction of tumorigenic p73 transcripts and proteins, importantly, without abolishing the wild-type p73 tumor suppressor form as observed with p73-shRNA. The specific antisense oligonucleotides rescued cells from apoptosis inhibition due to overexpression of their corresponding amino-truncated p73 isoform and decreased tumor cell proliferation. Furthermore, ASO-116 against DeltaEx2/3 coupled to magnetic nanobead polyethyleneimine (MNB/PEI) carriers significantly inhibited malignant melanoma growth, which correlated with a shift in the balance between endogenous TAp73 and DeltaEx2/3 towards apoptotic full-length p73.

conclusionOur study demonstrates the successful development of LNA-ASOs that selectively differentiate between the closely related p73 oncoproteins, and provide new tools to further delineate their biological properties in different human malignancies and for therapeutic cancer targeting.

Indexed as

Alternative SplicingAnimalsApoptosisBase SequenceBlotting, WesternCell LineCell Line, TumorDNA-Binding ProteinsFemaleGreen Fluorescent ProteinsHumansMelanoma, ExperimentalMiceMice, NudeMicroscopy, FluorescenceMolecular Sequence Datadelta Np73 protein, humanDNA-Binding ProteinsGreen Fluorescent ProteinsNuclear ProteinsOligonucleotides, AntisenseProtein IsoformsRNA, MessengerRNA, Small InterferingTP73 protein, humanTrp73 protein, mouseTumor Protein p73Tumor Suppressor Proteins

Identifiers

PMID19671150
PMCPMC2734544
OpenAlexW2163215020

What OpenQuestion holds

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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.