Evidence map›Paper›PMID 30596759›Full record

ArticlePloS one2018

A genetically engineered microRNA-34a prodrug demonstrates anti-tumor activity in a canine model of osteosarcoma.

Fernando Alegre, Amanda R Ormonde, Kellie M Snider, Kevin Woolard, Ai-Ming Yu, Luke A Wittenburg

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

16 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Osteosarcoma in a ceRNET perspective.Journal of biomedical science · 2024
    Review
  3. Review
  4. Review
  5. RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.The Journal of pharmacology and experimental therapeutics · 2023
    Review
  6. Review
  7. Article
  8. Navigating the genomic instability mine field of osteosarcoma to better understand implications of non-coding RNAs.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2022
    Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
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  16. 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

6 authors at 1 institution in 1 country.

Fernando AlegreDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.ORCID 0000-0003-1732-6309
Amanda R OrmondeDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Kellie M SniderDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Kevin WoolardDepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America.
Ai-Ming YuDepartment of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, California, United States of America.
Luke A WittenburgDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
University of California, Davis · US

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
Recombinant microRNAs in xenobiotic dispositionR01GM113888 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI YU, AIMING · 2016 to 2019
$1.3M
Defining the role of core binding factor protein interactions in osteosarcomaK01OD026526 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI WITTENBURG, LUKE A. · 2018 to 2022
$675k
NCI NIH HHS P30 CA093373NIGMS NIH HHS R01 GM113888NIH HHS K01 OD026526
6 · The paper itself

Abstract

Osteosarcoma (OSA) represents the most common primary bone tumor in humans and pet dogs. Little progress has been made with regard to viable treatment options in the past three decades and patients presenting with metastatic disease continue to have a poor prognosis. Recent mouse studies have suggested that microRNA-34a (miR-34a) may have anti-tumor activities in human OSA models. Due to the conservation of microRNA across species, we hypothesized that a bioengineered miR-34a prodrug (tRNA/miR-34a) would have similar effects in canine OSA, providing a valuable preclinical model for development of this therapeutic modality. Using a panel of canine OSA cell lines, we found that tRNA/miR-34a reduced viability, clonogenic growth, and migration and invasion while increasing tumor cell apoptosis. Furthermore, canine OSA cells successfully process the tRNA/miR-34a into mature miR-34a which reduces expression of target proteins such as platelet derived growth factor receptor alpha (PDGFRα), Notch1 and vascular endothelial growth factor (VEGF). Additionally, our subcutaneous OSA xenograft model demonstrated in vivo tumor growth delay, increased necrosis and apoptosis by tRNA/miR-34a, and decreased cellular proliferation ability. Taken together, these data support that this novel microRNA-based therapy may possess clinical utility in a spontaneously-occurring large animal model of OSA, which can then serve to inform the clinical development of this therapy for human OSA patients.

Indexed as

MicroRNAsOsteosarcomaAnimalsApoptosisCell LineageDogsGenetic EngineeringHumansNeoplasm ProteinsNeoplasms, ExperimentalProdrugsReceptor, Notch1Receptor, Platelet-Derived Growth Factor betaRNA, TransferMicroRNAsMIRN34 microRNA, humanNeoplasm ProteinsProdrugsReceptor, Notch1Receptor, Platelet-Derived Growth Factor betaRNA, Transfer

Identifiers

PMID30596759
PMCPMC6312226
OpenAlexW2907516726

What Socratic holds

Textmetadata
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 Socratic graph.