Evidence map›Paper›PMID 41147659›Full record

ArticleFEBS letters2026

Targeting EZH2 reverses thyroid cell dedifferentiation and enhances iodide uptake in anaplastic thyroid cancer.

Diego Claro de Mello, Marcella Maringolo Cristovão, Guilherme Henrique, Vinicius Gonçalves Rodrigues, Caroline Serrano-Nascimento, Edna Teruko Kimura, Cesar Seigi Fuziwara

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In one paragraph

Article in FEBS letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Genomics and Multi-Omics to Guide Clinical Management in Thyroid Cancer.International journal of molecular sciences · 2026
    Review
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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

7 authors.

Diego Claro de MelloDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo (USP), Brazil.ORCID 0000-0002-6405-0635
Marcella Maringolo CristovãoDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo (USP), Brazil.
Guilherme HenriqueDepartment of Medicine, Laboratory of Molecular and Translational Endocrinology Medicine, Federal University of São Paulo (UNIFESP), Brazil.
Vinicius Gonçalves RodriguesDepartment of Medicine, Laboratory of Molecular and Translational Endocrinology Medicine, Federal University of São Paulo (UNIFESP), Brazil.
Caroline Serrano-NascimentoDepartment of Medicine, Laboratory of Molecular and Translational Endocrinology Medicine, Federal University of São Paulo (UNIFESP), Brazil.
Edna Teruko KimuraDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo (USP), Brazil.
Cesar Seigi FuziwaraDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo (USP), Brazil.

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 311210/2021-0Conselho Nacional de Desenvolvimento Científico e Tecnológico 406997/2023-3Conselho Nacional de Desenvolvimento Científico e Tecnológico 409443/2021-2Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 88887.184496/2025-00Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 88887.372858/2019-00Fundação de Amparo à Pesquisa do Estado de São Paulo 2016/18517-8Fundação de Amparo à Pesquisa do Estado de São Paulo 2019/17282-5Fundação de Amparo à Pesquisa do Estado de São Paulo 2019/25116-8Fundação de Amparo à Pesquisa do Estado de São Paulo 2020/10403-9Fundação de Amparo à Pesquisa do Estado de São Paulo 2021/01674-1Fundação de Amparo à Pesquisa do Estado de São Paulo 2023/04452-5Fundação de Amparo à Pesquisa do Estado de São Paulo 2024/09472-7SBEM (Brazilian Society of Endocrinology and Metabolism)
6 · The paper itself

Abstract

Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy characterized by dedifferentiation and radioiodine refractoriness. We investigated whether EZH2-mediated H3K27me3 deposition represses thyroid differentiation genes (TDGs) in ATC cells. Online ChIP-seq analyses and CUT&RUN confirmed EZH2/H3K27me3 enrichment at key TDGs (SLC5A5, NKX2-1, TSHR, FOXE1, TPO). Pharmacological inhibition of EZH2 with EPZ6438 reactivated TDG expression in RAS and BRAF-mutated ATC cell lines and partially restored iodide uptake. Co-treatment with the MEK1/2 inhibitor U0126 further enhanced TDG expression, consistent with MAPK-dependent regulation of EZH2. These findings reveal EZH2 as a mediator of ATC dedifferentiation and highlight its inhibition as a potential strategy to restore thyroid function and sensitize tumors to radioiodine. Impact statement This study reveals how EZH2-driven epigenetic remodeling controls thyroid cell dedifferentiation and loss of iodide uptake in anaplastic thyroid cancer. Our findings provide new mechanistic insights and highlight an FDA-approved drug with repurposing potential, advancing both anaplastic thyroid cancer biology research and therapeutic perspectives.

Indexed as

Cell DedifferentiationEnhancer of Zeste Homolog 2 ProteinThyroid Carcinoma, AnaplasticThyroid GlandThyroid NeoplasmsCell Line, TumorGene Expression Regulation, NeoplasticHumansIodine RadioisotopesEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanIodine Radioisotopesanaplastic thyroid cancerEZH2iodide uptakeNISTazemetostatthyroid differentiation

Identifiers

PMID41147659
PMCPMC12834004

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Registered trials

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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.