Evidence map›Paper›PMID 23087083›Full record

ArticleCarcinogenesis2013

Recruitment of NCOR1 to VDR target genes is enhanced in prostate cancer cells and associates with altered DNA methylation patterns.

Craig L Doig, Prashant K Singh, Vineet K Dhiman, James L Thorne, Sebastiano Battaglia, Michelle Sobolewski, Orla Maguire, Laura P O'Neill, Bryan M Turner, Christopher J McCabe and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

35 citing papers in PubMed, 56 citations in OpenAlex.

  1. Trial
  2. The effect of 1,25(OH)Clinical epigenetics · 2025
    Article
  3. Micronutrient regulation of the DNA methylome.Frontiers in epigenetics and epigenomics · 2024
    Review
  4. Review
  5. Article
  6. Review
  7. 1α,25(OH)Journal for immunotherapy of cancer · 2022
    Article
  8. Nuclear Receptors and Lipid Sensing.Advances in experimental medicine and biology · 2022
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Cholesterol, Oxysterols and LXRs in Breast Cancer Pathophysiology.International journal of molecular sciences · 2020
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Vitamin D Receptor Signaling and Cancer.Endocrinology and metabolism clinics of North America · 2017
    Review
  19. Review
  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

12 authors at 4 institutions in 2 countries.

Craig L DoigDepartment of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Prashant K Singh
Vineet K Dhiman
James L Thorne
Sebastiano Battaglia
Michelle Sobolewski
Orla Maguire
Laura P O'Neill
Bryan M Turner
Christopher J McCabe
Dominic J Smiraglia
Moray J Campbell
University of Birmingham · GBRoswell Park Comprehensive Cancer Center · USCancer Genetics (United States) · USUniversity of Leeds · GB

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MARK G FRATTINI · 1985 to 2026
$116.6M
Vitamin D in Prostate Cancer: Tumor Vasculature EffectsR01CA095045 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI JOHNSON, CANDACE S · 2002 to 2012
$3.2M
Vitamin D Analogs for Chemoprevention of Prostate CAncerR01CA095367 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI FOSTER, BARBARA A. · 2002 to 2012
$3.2M
Cancer Research UK 14487Cancer Research UK C1015/A9077Medical Research Council MR/J001414/1NCI NIH HHS 2R01-CA-095045-06NCI NIH HHS CA016056NCI NIH HHS P30 CA016056NCI NIH HHS R01 CA095367-06
6 · The paper itself

Abstract

The current study investigated transcriptional distortion in prostate cancer cells using the vitamin D receptor (VDR) as a tool to examine how epigenetic events driven by corepressor binding and CpG methylation lead to aberrant gene expression. These relationships were investigated in the non-malignant RWPE-1 cells that were 1α,25(OH)(2)D(3) responsive (RWPE-1) and malignant cell lines that were 1α,25(OH)(2)D(3) partially responsive (RWPE-2) and resistant (PC-3). These studies revealed that selective attenuation and repression of VDR transcriptional responses in the cancer cell lines reflected their loss of antiproliferative sensitivity. This was evident in VDR target genes including VDR, CDKN1A (encodes p21( (waf1/cip1) )) and GADD45A; NCOR1 knockdown alleviated this malignant transrepression. ChIP assays in RWPE-1 and PC-3 cells revealed that transrepression of CDKN1A was associated with increased NCOR1 enrichment in response to 1α,25(OH)(2)D(3) treatment. These findings supported the concept that retained and increased NCOR1 binding, associated with loss of H3K9ac and increased H3K9me2, may act as a beacon for the initiation and recruitment of DNA methylation. Overexpressed histone methyltransferases (KMTs) were detectable in a wide panel of prostate cancer cell lines compared with RWPE-1 and suggested that generation of H3K9me2 states would be favored. Cotreatment of cells with the KMT inhibitor, chaetocin, increased 1α,25(OH)(2)D(3)-mediated induction of CDKN1A expression supporting a role for this event to disrupt CDKN1A regulation. Parallel surveys in PC-3 cells of CpG methylation around the VDR binding regions on CDKN1A revealed altered basal and VDR-regulated DNA methylation patterns that overlapped with VDR-induced recruitment of NCOR1 and gene transrepression. Taken together, these findings suggest that sustained corepressor interactions with nuclear-resident transcription factors may inappropriately transform transient-repressive histone states into more stable and repressive DNA methylation events.

Indexed as

DNA MethylationGene Expression Regulation, NeoplasticApoptosisBone Density Conservation AgentsCalcitriolCell ProliferationCells, CulturedChromatin ImmunoprecipitationCyclin-Dependent Kinase Inhibitor p21Drug Resistance, NeoplasmEpigenesis, GeneticHumansMaleNuclear Receptor Co-Repressor 1Promoter Regions, GeneticProstateBone Density Conservation AgentsCalcitriolCyclin-Dependent Kinase Inhibitor p21NCOR1 protein, humanNuclear Receptor Co-Repressor 1Receptors, CalcitriolRNA, Messenger

Identifiers

PMID23087083
PMCPMC3564435
OpenAlexW2167276745

What OpenQuestion holds

Textmetadata
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.