Evidence map›Paper›PMID 24243688›Full record

ArticleEndocrine-related cancer2014

Histone deacetylation of NIS promoter underlies BRAF V600E-promoted NIS silencing in thyroid cancer.

Zongjing Zhang, Dingxie Liu, Avaniyapuram Kannan Murugan, Zhimin Liu, Mingzhao Xing

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrine-related cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 4 pooled it
3.7field-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

59 citing papers in PubMed, 4 syntheses or guidelines pooled it, 101 citations in OpenAlex.

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  11. Endocrine oncology (Bristol, England) · 2026
    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

5 authors at 3 institutions in 2 countries.

Zongjing ZhangDivision of Endocrinology, Diabetes, and Metabolism, Laboratory for Cellular and Molecular Thyroid Research, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA Department of Endocrinology and Metabolism, Changzheng Hospital, the Second Military Medical University, Shanghai, China.
Dingxie Liu
Avaniyapuram Kannan Murugan
Zhimin Liu
Mingzhao Xing
Johns Hopkins Medicine · USJohns Hopkins University · USSecond Military Medical University · CN

Funding

Genetic & Epigenetic Events in Papillary Thyroid CancerR01CA113507 · NCI · JOHNS HOPKINS UNIVERSITY · PI XING, MICHAEL MINGZHAO · 2006 to 2015
$2.2M
NCI NIH HHS R01 CA113507
6 · The paper itself

Abstract

The BRAF V600E mutation causes impaired expression of sodium iodide symporter (NIS) and radioiodine refractoriness of thyroid cancer, but the underlying mechanism remains undefined. In this study, we hypothesized that histone deacetylation at the NIS (SLC5A5) promoter was the mechanism. Using the chromatin immunoprecipitation approach, we examined histone acetylation status on the lysine residues H3K9/14, H3K18, total H4, and H4K16 at the NIS promoter under the influence of BRAF V600E. We found that expression of stably or transiently transfected BRAF V600E inhibited NIS expression while the deacetylase inhibitor SAHA stimulated NIS expression in PCCL3 rat thyroid cells. Although BRAF V600E enhanced global histone acetylation, it caused histone deacetylation at the NIS promoter while SAHA caused acetylation in the cells. In human thyroid cancer BCPAP cells harboring homozygous BRAF V600E mutation, BRAF V600E inhibitor, PLX4032, and MEK inhibitor, AZD6244, increased histone acetylation of the NIS promoter, suggesting that BRAF V600E normally maintained histone in a deacetylated state at the NIS promoter. The regions most commonly affected with deacetylation by BRAF V600E were the transcriptionally active areas upstream of the translation start that contained important transcription factor binding sites, including nucleotides -297/-107 in the rat NIS promoter and -692/-370 in the human NIS promoter. Our findings not only reveal an epigenetic mechanism for BRAF V600E-promoted NIS silencing involving histone deacetylation at critical regulatory regions of the NIS promoter but also provide further support for our previously proposed combination therapy targeting major signaling pathways and histone deacetylase to restore thyroid gene expression for radioiodine treatment of thyroid cancer.

Indexed as

AcetylationAnimalsCell LineCell Line, TumorGene SilencingHistonesHumansMutationPromoter Regions, GeneticProto-Oncogene Proteins B-rafRatsSodium-Iodide SymportersSymportersThyroid NeoplasmsHistonesProto-Oncogene Proteins B-rafSodium-Iodide SymportersSymportersBRAF V600E mutationhistone acetylationhistone deacetylationNIS generadioiodinethyroid cancer

Identifiers

PMID24243688
PMCPMC3920838
OpenAlexW2117574089

What OpenQuestion holds

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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.