Evidence map›Paper›PMID 20054818›Full record

ArticleThe Prostate2010

Methylation of a single intronic CpG mediates expression silencing of the PMP24 gene in prostate cancer.

Xiang Zhang, Mengchu Wu, Hong Xiao, Ming-Tsung Lee, Linda Levin, Yuet-Kin Leung, Shuk-Mei Ho

Abstract read
In one paragraph

Article in The Prostate, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

42 citing papers in PubMed, 69 citations in OpenAlex.

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  17. Peroxisomal Metabolite and Cofactor Transport in Humans.Frontiers in cell and developmental biology · 2020
    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 at 2 institutions in 2 countries.

Xiang ZhangDepartment of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Mengchu Wu
Hong Xiao
Ming-Tsung Lee
Linda Levin
Yuet-Kin Leung
Shuk-Mei Ho
University of Cincinnati Medical Center · USNational University Cancer Institute, Singapore · SG

Funding

REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY RESEARCHP30ES006096 · NIEHS · UNIVERSITY OF CINCINNATI · PI YADAV, JAGJIT S · 1992 to 2022
$35.4M
Epigenetic Basis for Prostate Carcinogenesis following Early Estrogenic ExposuresR01ES015584 · NIEHS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI HO, SHUK-MEI, PRINS, GAIL S · 2008 to 2012
$3.1M
PROSTATIC DIFFERENTIATION &SEX HORMONE METABOLISMR01CA015776 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI HO, SHUK-MEI · 1987 to 2008
$1.8M
Hormone-induced inflammation and prostate cancerR01CA112532 · NCI · UNIVERSITY OF CINCINNATI · PI HO, SHUK-MEI · 2006 to 2009
$1.1M
NCI NIH HHS CA112532NCI NIH HHS CA15776NCI NIH HHS R01 CA015776NCI NIH HHS R01 CA112532NIEHS NIH HHS ES006096NIEHS NIH HHS ES015584NIEHS NIH HHS P30 ES006096NIEHS NIH HHS R01 ES015584
6 · The paper itself

Abstract

backgroundWe previously demonstrated that a putative anti-tumor gene, peroxisomal membrane protein 4, 24 kDa (PMP24 or PXMP4), is silenced via DNA methylation of a CpG island in its 5' flanking region (5'-CGI) in prostate cancer (PCa) cells.

methodsTo identify demethylation hypersensitive site(s) in PMP24 5'-CGI, PC-3 cells with methylated 5'-CGI were treated with a low-dose of 5-aza-2'-deoxycytidine (5-aza-dC) just sufficient to reactivate gene expression, referred as the limited demethylation approach. Gel shift assays and promoter analyzes were performed to demonstrate the role of the hypersensitive site in PMP24 gene regulation. Transfection of a methylated oligonucleotide corresponding to the hypersensitive site was conducted to determine the effect of site-specific methylation on the gene expression. Bisulfite sequencing analysis was performed to reveal the methylation status of PMP24 promoter in cultured cells and microdissected samples. In situ hybridization was applied to determine expression positivity of PMP24 mRNA.

resultsA 5-aza-dC hypersensitive site encompasses two CpG dinucleotides in intron 1 was identified. Methylation of the first, but not the second, CpG dinucleotide of this site disrupted DNA-protein interactions and suppressed the gene expression. Using archival specimens, we found the first CpG dinucleotide of the hypersensitive site is hypermethylated with a loss of PMP24 mRNA expression in microdissected PCa cells when compared to normal prostatic epithelial cells.

conclusionsThese findings support a critical role for a single intronic CpG dinucleotide in PMP24 gene regulation through DNA methylation. The data suggest that methylation-mediated silencing of PMP24 is a molecular event associated with prostate carcinogenesis.

Indexed as

Cell Line, TumorCells, CulturedCpG IslandsDNA MethylationElectrophoretic Mobility Shift AssayGene SilencingHumansIn Situ HybridizationIntronsMembrane ProteinsPromoter Regions, GeneticReverse Transcriptase Polymerase Chain ReactionMembrane ProteinsPXMP4 protein, human

Identifiers

PMID20054818
PMCPMC2857536
OpenAlexW2098566626

What OpenQuestion holds

Textmetadata
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.