Evidence map›Paper›PMID 22144423›Full record

ArticleCancer prevention research (Philadelphia, Pa.)2012

ALDH1A1 is a novel EZH2 target gene in epithelial ovarian cancer identified by genome-wide approaches.

Hua Li, Benjamin G Bitler, Vinod Vathipadiekal, Marie E Maradeo, Michael Slifker, Caretha L Creasy, Peter J Tummino, Paul Cairns, Michael J Birrer, Rugang Zhang

Open access · greenAbstract read
In one paragraph

Article in Cancer prevention research (Philadelphia, Pa.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 51 citations in OpenAlex.

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  14. Stemness-Related Markers in Cancer.Cancer translational medicine · 2017
    Article
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  18. H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2015
    Article
  19. Article
  20. 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

10 authors at 3 institutions in 1 country.

Hua LiWomen's Cancer Program and Epigenetics and Progenitor Cell Keystone Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Benjamin G Bitler
Vinod Vathipadiekal
Marie E Maradeo
Michael Slifker
Caretha L Creasy
Peter J Tummino
Paul Cairns
Michael J Birrer
Rugang Zhang
Fox Chase Cancer Center · USGlaxoSmithKline (United States) · USMassachusetts General Hospital · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
Therapeutic Micro RNA Strategies for Ovarian CancerP50CA083638 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI GODWIN, ANDREW K., GOLEMIS, ERICA A. · 1999 to 2013
$33.6M
TRAINING PROGRAM IN CANCER RESEARCHT32CA009035 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CHERNOFF, JONATHAN · 1985 to 2020
$10.5M
Targeting EZH2 in CARM1-expressing epithelial ovarian cancerR01CA163377 · NCI · WISTAR INSTITUTE · PI ZHANG, RUGANG · 2012 to 2021
$3.7M
NCI NIH HHS CA-009035-35NCI NIH HHS P30 CA006927NCI NIH HHS P50 CA083638NCI NIH HHS R01 CA163377NCI NIH HHS T32 CA009035
6 · The paper itself

Abstract

Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in the United States. EZH2 silences gene expression through trimethylating lysine 27 on histone H3 (H3K27Me3). EZH2 is often overexpressed in EOC and has been suggested as a target for EOC intervention. However, EZH2 target genes in EOC remain poorly understood. Here, we mapped the genomic loci occupied by EZH2/H3K27Me3 using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) and globally profiled gene expression in EZH2-knockdown EOC cells. Cross-examination of gene expression and ChIP-seq revealed a list of 60 EZH2 direct target genes whose expression was upregulated more than 1.5-fold upon EZH2 knockdown. For three selected genes (ALDH1A1, SSTR1, and DACT3), we validated their upregulation upon EZH2 knockdown and confirmed the binding of EZH2/H3K27Me3 to their genomic loci. Furthermore, the presence of H3K27Me3 at the genomic loci of these EZH2 target genes was dependent upon EZH2. Interestingly, expression of ALDH1A1, a putative marker for EOC stem cells, was significantly downregulated in high-grade serous EOC (n = 53) compared with ovarian surface epithelial cells (n = 10, P < 0.001). Notably, expression of ALDH1A1 negatively correlated with expression of EZH2 (n = 63, Spearman r = -0.41, P < 0.001). Thus, we identified a list of 60 EZH2 target genes and established that ALDH1A1 is a novel EZH2 target gene in EOC cells. Our results suggest a role for EZH2 in regulating EOC stem cell equilibrium via regulation of ALDH1A1 expression.

Indexed as

Aldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyBiomarkers, TumorBlotting, WesternCell Line, TumorChromatin ImmunoprecipitationDNA-Binding ProteinsEnhancer of Zeste Homolog 2 ProteinFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansOligonucleotide Array Sequence AnalysisOvarian NeoplasmsPolycomb Repressive Complex 2Real-Time Polymerase Chain ReactionAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyALDH1A1 protein, humanBiomarkers, TumorDNA-Binding ProteinsEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanPolycomb Repressive Complex 2Retinal DehydrogenaseRNA, MessengerRNA, Small InterferingTranscription Factors

Identifiers

PMID22144423
PMCPMC3294119
OpenAlexW2132368597

What OpenQuestion holds

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LicenceTDM
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.