Evidence map›Paper›PMID 27155790›Full record

ArticleMolecular oncology2016

miR-200c and phospho-AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis.

Pablo Berlanga, Lisandra Muñoz, Marta Piqueras, J Antoni Sirerol, María Dolors Sánchez-Izquierdo, David Hervás, Miguel Hernández, Margarita Llavador, Isidro Machado, Antonio Llombart-Bosch and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
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  5. APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b.Cellular and molecular life sciences : CMLS · 2022
    Article
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  8. Bioengineered · 2022
    Article
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  10. Differential gene expression analysis for osteosarcoma lung metastases.Cancer biomarkers : section A of Disease markers · 2022
    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

13 authors at 5 institutions in 1 country.

Pablo BerlangaPediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, Spain; Clinical and Translational Research in Cancer, Instituto de Investigación Sanitaria La Fe, Spain.
Lisandra MuñozLaboratory of Cellular and Molecular Biology, Instituto de Investigación Sanitaria La Fe, Spain.
Marta PiquerasLaboratory of Cellular and Molecular Biology, Instituto de Investigación Sanitaria La Fe, Spain.
J Antoni SirerolLaboratory of Cellular and Molecular Biology, Instituto de Investigación Sanitaria La Fe, Spain.
María Dolors Sánchez-IzquierdoGenomics Unit, Instituto de Investigación Sanitaria La Fe, Spain.
David HervásBiostatistics Unit, Instituto de Investigación Sanitaria La Fe, Spain.
Miguel HernándezDepartment of Pathology, Hospital La Fe, Spain.
Margarita LlavadorDepartment of Pathology, Hospital La Fe, Spain.
Isidro MachadoDepartment of Pathology, Instituto Valenciano de Oncología, Spain.
Antonio Llombart-BoschDepartment of Pathology, University of Valencia, Spain.
Adela CañetePediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, Spain; Clinical and Translational Research in Cancer, Instituto de Investigación Sanitaria La Fe, Spain.
Victoria CastelPediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, Spain; Clinical and Translational Research in Cancer, Instituto de Investigación Sanitaria La Fe, Spain.
Jaime Font de MoraClinical and Translational Research in Cancer, Instituto de Investigación Sanitaria La Fe, Spain; Laboratory of Cellular and Molecular Biology, Instituto de Investigación Sanitaria La Fe, Spain. Electronic address: jaime.fontdemora@gmail.com.
Instituto de Investigación Sanitaria La Fe · ESHospital Universitari i Politècnic La Fe · ESLeitat Technological Center · ESFundación Instituto Valenciano de Oncología · ESUniversitat de València · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lung metastasis is the major cause of death in osteosarcoma patients. However, molecular mechanisms underlying this metastasis remain poorly understood. To identify key molecules related with pulmonary metastasis of pediatric osteosarcomas, we analyzed high-throughput miRNA expression in a cohort of 11 primary tumors and 15 lung metastases. Results were further validated with an independent cohort of 10 primary tumors and 6 metastases. In parallel, we performed immunohistochemical analysis of activated signaling pathways in 36 primary osteosarcomas. Only phospho-AKT associated with lower overall survival in primary tumors, supporting its role in osteosarcoma progression. CTNNB1 expression also associated with lower overall survival but was not strong enough to be considered an independent variable. Interestingly, miR-200c was overexpressed in lung metastases, implicating an inhibitory feed-back loop to PI3K-AKT. Moreover, transfection of miR200c-mimic in U2-OS cells reduced phospho-AKT levels but increased cellular migration and proliferation. Notably, miR-200c expression strongly correlated with miR-141 and with the osteogenic inhibitor miR-375, all implicated in epithelial to mesenchymal transition. These findings contrast epithelial tumors where reduced miR-200c expression promotes metastasis. Indeed, we noted that osteosarcoma cells in the lung also expressed the epithelial marker CDH1, revealing a change in their mesenchymal phenotype. We propose that miR-200c upregulation occurs late in osteosarcoma progression to provide cells with an epithelial phenotype that facilitates their integration in the metastatic lung niche. Thus, our findings identify phospho-AKT in the primary tumor and miR-200c later during tumor progression as prognostic molecules and potential therapeutic targets to prevent progression and metastasis of pediatric osteosarcomas.

Indexed as

Disease ProgressionAdolescentAntigens, CDBiomarkers, TumorCadherinsCell Line, TumorCell MovementCell ProliferationChildCohort StudiesEnzyme ActivationEpithelial CellsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansAntigens, CDBiomarkers, TumorCadherinsCDH1 protein, humanMicroRNAsMIRN200 microRNA, humanProto-Oncogene Proteins c-aktLung metastasisMesenchymal to epithelial transitionmiR-200cPediatric osteosarcomaPhospho-AKT

Identifiers

PMID27155790
PMCPMC5423177
OpenAlexW2336414313

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.