Evidence map›Paper›PMID 27764816›Full record

ArticleOncotarget2016

DNMT3B in vitro knocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation.

Francesca Megiorni, Simona Camero, Simona Ceccarelli, Heather P McDowell, Olga Mannarino, Francesco Marampon, Barry Pizer, Rajeev Shukla, Antonio Pizzuti, Cinzia Marchese and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

32 citing papers in PubMed, 40 citations in OpenAlex.

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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

12 authors at 3 institutions in 2 countries.

Francesca MegiorniDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Simona CameroDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Simona CeccarelliDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Heather P McDowellDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Olga MannarinoDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Francesco MaramponDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Barry PizerDepartment of Oncology, Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
Rajeev ShuklaDepartment of Perinatal and Paediatric Pathology, Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
Antonio PizzutiDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Cinzia MarcheseDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Anna ClericoDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Carlo DominiciDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Sapienza University of Rome · ITAlder Hey Children's NHS Foundation Trust · GBUniversity of L'Aquila · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27. DNMT3B depletion also impaired RB phosphorylation status and decreased migratory capacity and clonogenic potential. Interestingly, DNMT3B knock-down was able to commit ERMS cells towards myogenic terminal differentiation, as confirmed by the acquisition of a myogenic-like phenotype and by the increased expression of the myogenic markers MYOD1, Myogenin and MyHC. Finally, inhibition of MEK/ERK signalling by U0126 resulted in a reduction of DNMT3B protein, giving evidence that DNMT3B is a down-stream molecule of this oncogenic pathway.Taken together, our data indicate that altered expression of DNMT3B plays a key role in ERMS development since its silencing is able to reverse cell cancer phenotype by rescuing myogenic program. Epigenetic therapy, by targeting the DNA methylation machinery, may represent a novel therapeutic strategy against RMS.

Indexed as

Down-RegulationButadienesCell CycleCell DifferentiationCell Line, TumorCell ProliferationDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansIn Vitro TechniquesMuscle Fibers, SkeletalNitrilesPhenotypeRhabdomyosarcoma, AlveolarButadienesDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BNitrilesU 0126DNMT3BMEK/ERK signallingmyogenic differentiationrhabdomyosarcomaRNA interference

Identifiers

PMID27764816
PMCPMC5346718
OpenAlexW2531060677

What OpenQuestion 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 OpenQuestion graph.