Evidence map›Paper›PMID 23333711›Full record

ArticleGastroenterology2013

Hypomethylation of noncoding DNA regions and overexpression of the long noncoding RNA, AFAP1-AS1, in Barrett's esophagus and esophageal adenocarcinoma.

Wenjing Wu, Tushar D Bhagat, Xue Yang, Jee Hoon Song, Yulan Cheng, Rachana Agarwal, John M Abraham, Sariat Ibrahim, Matthias Bartenstein, Zulfiqar Hussain and 7 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 4 pooled it
8.7field-weighted citation impact, top 2% 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

147 citing papers in PubMed, 4 syntheses or guidelines pooled it, 232 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. AFAP1-AS1 regulates oral squamous cell carcinoma development through the miR-93-3p/CCND1 signaling pathway.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
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  19. Improving outcomes in patients with oesophageal cancer.Nature reviews. Clinical oncology · 2023
    Review
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87 more citing papers are in PubMed but not listed here.

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

17 authors at 5 institutions in 2 countries.

Wenjing WuCenter for Laboratory Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Tushar D Bhagat
Xue Yang
Jee Hoon Song
Yulan Cheng
Rachana Agarwal
John M Abraham
Sariat Ibrahim
Matthias Bartenstein
Zulfiqar Hussain
Masako Suzuki
Yiting Yu
Wei Chen
Charis Eng
John Greally
Amit Verma
Stephen J Meltzer
Albert Einstein College of Medicine · USSidney Kimmel Comprehensive Cancer Center · USFirst Affiliated Hospital of Xi'an Jiaotong University · CNCleveland Clinic · USJohns Hopkins University · US

Funding

The temporal epigenomic program of Barrett's neoplastic progressionR01DK087454 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI MELTZER, STEPHEN J · 2009 to 2013
$1.8M
Inflammatory Bowel Disease-Associated Malignant TransformationR01CA133012 · NCI · JOHNS HOPKINS UNIVERSITY · PI MELTZER, STEPHEN J · 2009 to 2013
$1.5M
The Role of microRNA Alterations in Barrett's CarcinogenesisR01CA146799 · NCI · JOHNS HOPKINS UNIVERSITY · PI MELTZER, STEPHEN J · 2009 to 2012
$1.3M
NCI NIH HHS CA133012NCI NIH HHS CA146799NCI NIH HHS R01 CA133012NCI NIH HHS R01 CA146799NIDDK NIH HHS DK087454NIDDK NIH HHS R01 DK087454
6 · The paper itself

Abstract

BACKGROUND &

aimsAlterations in methylation of protein-coding genes are associated with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Dysregulation of noncoding RNAs occurs during carcinogenesis but has never been studied in BE or EAC. We applied high-resolution methylome analysis to identify changes at genomic regions that encode noncoding RNAs in BE and EAC.

methodsWe analyzed methylation of 1.8 million CpG sites using massively parallel sequencing-based HELP tagging in matched EAC, BE, and normal esophageal tissues. We also analyzed human EAC (OE33, SKGT4, and FLO-1) and normal (HEEpic) esophageal cells.

resultsBE and EAC exhibited genome-wide hypomethylation, significantly affecting intragenic and repetitive genomic elements as well as noncoding regions. These methylation changes targeted small and long noncoding regions, discriminating normal from matched BE or EAC tissues. One long noncoding RNA, AFAP1-AS1, was extremely hypomethylated and overexpressed in BE and EAC tissues and EAC cells. Its silencing by small interfering RNA inhibited proliferation and colony-forming ability, induced apoptosis, and reduced EAC cell migration and invasion without altering the expression of its protein-coding counterpart, AFAP1.

conclusionsBE and EAC exhibit reduced methylation that includes noncoding regions. Methylation of the long noncoding RNA AFAP1-AS1 is reduced in BE and EAC, and its expression inhibits cancer-related biologic functions of EAC cells.

Indexed as

Gene Expression Regulation, NeoplasticAdenocarcinomaBarrett EsophagusCell Line, TumorCell ProliferationCell Transformation, NeoplasticDNA MethylationDNA, NeoplasmEsophageal NeoplasmsHumansMicrofilament ProteinsPromoter Regions, GeneticRNA, Long NoncodingRNA, Small InterferingAFAP1 protein, humanDNA, NeoplasmMicrofilament ProteinsRNA, Long NoncodingRNA, Small Interfering

Identifiers

PMID23333711
PMCPMC3739703
OpenAlexW2012045205

What OpenQuestion holds

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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.