Evidence map›Paper›PMID 26003733›Full record

ArticleBiochimica et biophysica acta2015

Epigenetic control of EMT/MET dynamics: HNF4α impacts DNMT3s through miRs-29.

Carla Cicchini, Valeria de Nonno, Cecilia Battistelli, Angela Maria Cozzolino, Marco De Santis Puzzonia, Silvia Anna Ciafrè, Chad Brocker, Frank J Gonzalez, Laura Amicone, Marco Tripodi

Open access · hybridAbstract read
In one paragraph

Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

48 citing papers in PubMed, 64 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026
    Review
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  7. Article
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  9. The lncRNA HOTAIR: a pleiotropic regulator of epithelial cell plasticity.Journal of experimental & clinical cancer research : CR · 2023
    Review
  10. Article
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  12. Male Factors: the Role of Sperm in Preimplantation Embryo Quality.Reproductive sciences (Thousand Oaks, Calif.) · 2021
    Review
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  15. 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

10 authors at 5 institutions in 2 countries.

Carla CicchiniIstituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Rome, Italy. Electronic address: cicchini@bce.uniroma1.it.
Valeria de NonnoIstituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Rome, Italy.
Cecilia BattistelliIstituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Rome, Italy.
Angela Maria CozzolinoNational Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
Marco De Santis PuzzoniaIstituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Rome, Italy.
Silvia Anna CiafrèDepartment of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Chad BrockerLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Frank J GonzalezLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Laura AmiconeIstituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Rome, Italy.
Marco TripodiIstituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Rome, Italy; National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy. Electronic address: tripodi@bce.uniroma1.it.
Sapienza University of Rome · ITCenter for Cancer Research · USIstituti di Ricovero e Cura a Carattere Scientifico · ITNational Institutes of Health · USUniversity of Rome Tor Vergata · IT

Funding

Xenobiotic receptorsZIABC005562 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK J · 2009 to 2025
$26.9M
TRANSCRIPTIONAL REGULATION OF GENES ENCODING XENOBIOTIC METABOLIZING ENZYMESZ01BC005561 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK · 1996 to 2008
$754k
Intramural NIH HHS Z01 BC005561
6 · The paper itself

Abstract

BACKGROUND AND

aimsEpithelial-to-mesenchymal transition (EMT) and the reverse mesenchymal-to-epithelial transition (MET) are manifestations of cellular plasticity that imply a dynamic and profound gene expression reprogramming. While a major epigenetic code controlling the coordinated regulation of a whole transcriptional profile is guaranteed by DNA methylation, DNA methyltransferase (DNMT) activities in EMT/MET dynamics are still largely unexplored. Here, we investigated the molecular mechanisms directly linking HNF4α, the master effector of MET, to the regulation of both de novo of DNMT 3A and 3B.

methodsCorrelation among EMT/MET markers, microRNA29 and DNMT3s expression was evaluated by RT-qPCR, Western blotting and immunocytochemical analysis. Functional roles of microRNAs and DNMT3s were tested by anti-miRs, microRNA precursors and chemical inhibitors. ChIP was utilized for investigating HNF4α DNA binding activity.

resultsHNF4α silencing was sufficient to induce positive modulation of DNMT3B, in in vitro differentiated hepatocytes as well as in vivo hepatocyte-specific Hnf4α knockout mice, and DNMT3A, in vitro, but not DNMT1. In exploring the molecular mechanisms underlying these observations, evidence have been gathered for (i) the inverse correlation between DNMT3 levels and the expression of their regulators miR-29a and miR-29b and (ii) the role of HNF4α as a direct regulator of miR-29a-b transcription. Notably, during TGFβ-induced EMT, DNMT3s' pivotal function has been proved, thus suggesting the need for the repression of these DNMTs in the maintenance of a differentiated phenotype.

conclusionsHNF4α maintains hepatocyte identity by regulating miR-29a and -29b expression, which in turn control epigenetic modifications by limiting DNMT3A and DNMT3B levels.

Indexed as

AnimalsCell DifferentiationCells, CulturedCell Transformation, NeoplasticCellular ReprogrammingDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AEpigenesis, GeneticEpithelial-Mesenchymal TransitionGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 4HepatocytesMiceMice, KnockoutMicroRNAsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADnmt3a protein, mouseHepatocyte Nuclear Factor 4Hnf4a protein, mouseMicroRNAsMIRN29 microRNA, mouseDe novo DNA methylationEpithelial–mesenchymal transitionHepatocytemiR-29TGFβ

Identifiers

PMID26003733
PMCPMC6319628
OpenAlexW1839314511

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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.