Evidence map›Paper›PMID 29123240›Full record

ArticleScientific reports2017

DNA methylation regulates TMEM16A/ANO1 expression through multiple CpG islands in head and neck squamous cell carcinoma.

Andrey Finegersh, Scott Kulich, Theresa Guo, Alexander V Favorov, Elana J Fertig, Ludmila V Danilova, Daria A Gaykalova, Joseph A Califano, Umamaheswar Duvvuri

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 19% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Role of ANO1 in tumors and tumor immunity.Journal of cancer research and clinical oncology · 2022
    Review
  7. TMEM16A as a potential treatment target for head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022
    Review
  8. Article
  9. Ion Channel Dysregulation in Head and Neck Cancers: Perspectives for Clinical Application.Reviews of physiology, biochemistry and pharmacology · 2021
    Review
  10. The Prognostic Value and Mechanisms of TMEM16A in Human Cancer.Frontiers in molecular biosciences · 2021
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1.Medical science monitor : international medical journal of experimental and clinical research · 2018
    Article
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

9 authors at 5 institutions in 2 countries.

Andrey FinegershDepartment of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Scott KulichVA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
Theresa GuoDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alexander V FavorovDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Elana J FertigDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ludmila V DanilovaDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Daria A GaykalovaDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joseph A CalifanoDivision of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, CA, USA.
Umamaheswar DuvvuriDepartment of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. duvvuriu@upmc.edu.
Johns Hopkins University · USJohns Hopkins Medicine · USVA Pittsburgh Healthcare System · USUniversity of California, San Diego · USUniversity of Pittsburgh · US

Funding

RESEARCH TRAINING IN OTOLARYNGOLOGYT32DC000027 · NIDCD · JOHNS HOPKINS UNIVERSITY · PI CAREY, JOHN PATRICK · 1989 to 2023
$5.5M
Epigenetic Biomarker Discovery in HPV Related HNSCCR01DE023347 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CALIFANO, JOSEPH A · 2013 to 2017
$1.9M
Dynamical Models of Cetuximab Resistance in HNSCC Based on Serial Genomics DataR01CA177669 · NCI · JOHNS HOPKINS UNIVERSITY · PI FERTIG, ELANA · 2014 to 2019
$1.8M
Paternal preconception alcohol on epigenetics and offspring drinkingF30AA021632 · NIAAA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FINEGERSH, ANDREY · 2013 to 2015
$143k
Novel targets to treat head and neck cancer in VeteransI01BX003456 · VA · VETERANS HEALTH ADMINISTRATION · PI DUVVURI, UMAMAHESWAR · 2017 to 2021
–
BLRD VA I01 BX003456NCI NIH HHS R01 CA177669NIAAA NIH HHS F30 AA021632NIDCD NIH HHS T32 DC000027NIDCR NIH HHS R01 DE023347
6 · The paper itself

Abstract

ANO1 is a calcium-activated chloride channel that is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and other cancers. While ANO1 expression negatively correlates with survival in several cancers, its epigenetic regulation is poorly understood. We analyzed HNSCC samples from TCGA and a separate dataset of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples to identify differentially methylated regions. E6 and E7 transfected normal oral keratinocytes (NOK) were used to induce hypermethylation of the ANO1 promoter. We found three CpG islands that correlated with ANO1 expression, including two positively correlated with expression. Using two HNSCC datasets with differential expression of ANO1, we showed hypermethylation of positively correlated CpG islands potentiates ANO1 expression. E7 but not E6 transfection of NOK cells led to hypermethylation of a positively correlated CpG island without a change in ANO1 expression. ANO1 promoter methylation was also correlated with patient survival. Our results are the first to show the contribution of positively correlated CpG's for regulating gene expression in HNSCC. Hypermethylation of the ANO1 promoter was strongly correlated with but not sufficient to increase ANO1 expression, suggesting methylation of positively correlated CpG's likely serves as an adjunct to other mechanisms of ANO1 activation.

Indexed as

CpG IslandsDNA MethylationEpigenesis, GeneticAnoctamin-1Carcinoma, Squamous CellHead and Neck NeoplasmsHumansNeoplasm ProteinsPromoter Regions, GeneticANO1 protein, humanAnoctamin-1Neoplasm Proteins

Identifiers

PMID29123240
PMCPMC5680248
OpenAlexW2765804020

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.