Evidence map›Paper›PMID 23403032›Full record

ArticleGenome research2013

A genome-wide RNA interference screen identifies new regulators of androgen receptor function in prostate cancer cells.

Keren Imberg-Kazdan, Susan Ha, Alex Greenfield, Christopher S Poultney, Richard Bonneau, Susan K Logan, Michael J Garabedian

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2013. 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
–field-weighted citation impact
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, 41 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Cells · 2021
    Review
  7. The role of mediator complex subunit 19 in human diseases.Experimental biology and medicine (Maywood, N.J.) · 2021
    Review
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  11. Review
  12. Article
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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 1 country.

Keren Imberg-KazdanDepartment of Biochemistry, New York University School of Medicine, New York, New York 10016, USA.
Susan Ha
Alex Greenfield
Christopher S Poultney
Richard Bonneau
Susan K Logan
Michael J Garabedian
New York Genome Center · USNew York University · US

Funding

Nanomedicine development center for mechanobiologyPN2EY016586 · NEI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DUSTIN, MICHAEL LORAN · 2005 to 2014
$23.0M
New collections of dsRNAs and overexpression miRNA constructs to supplement RNAiR01GM067761 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI PERRIMON, NORBERT · 2003 to 2019
$15.5M
TRANS-NETWORK PROJECTSU54CA143907 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GROSS, MITCHELL E · 2009 to 2013
$15.2M
Transcription repression in prostate cancerR01CA112226 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI LOGAN, SUSAN K. · 2008 to 2019
$4.2M
Center for Mechanotransduction and Nanomedicine. (RMI)PN1EY016586 · NEI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SHEETZ, MICHAEL PATRICK · 2004 to 2004
$81k
NCI NIH HHS CA112226NCI NIH HHS CA143907NCI NIH HHS R01 CA112226NCI NIH HHS U54 CA143907NEI NIH HHS EY016586NEI NIH HHS PN1 EY016586NEI NIH HHS PN2 EY016586NIGMS NIH HHS R01 GM067761
6 · The paper itself

Abstract

The androgen receptor (AR) is a mediator of both androgen-dependent and castration-resistant prostate cancers. Identification of cellular factors affecting AR transcriptional activity could in principle yield new targets that reduce AR activity and combat prostate cancer, yet a comprehensive analysis of the genes required for AR-dependent transcriptional activity has not been determined. Using an unbiased genetic approach that takes advantage of the evolutionary conservation of AR signaling, we have conducted a genome-wide RNAi screen in Drosophila cells for genes required for AR transcriptional activity and applied the results to human prostate cancer cells. We identified 45 AR-regulators, which include known pathway components and genes with functions not previously linked to AR regulation, such as HIPK2 (a protein kinase) and MED19 (a subunit of the Mediator complex). Depletion of HIPK2 and MED19 in human prostate cancer cells decreased AR target gene expression and, importantly, reduced the proliferation of androgen-dependent and castration-resistant prostate cancer cells. We also systematically analyzed additional Mediator subunits and uncovered a small subset of Mediator subunits that interpret AR signaling and affect AR-dependent transcription and prostate cancer cell proliferation. Importantly, targeting of HIPK2 by an FDA-approved kinase inhibitor phenocopied the effect of depletion by RNAi and reduced the growth of AR-positive, but not AR-negative, treatment-resistant prostate cancer cells. Thus, our screen has yielded new AR regulators including drugable targets that reduce the proliferation of castration-resistant prostate cancer cells.

Indexed as

Genome-Wide Association StudyRNA InterferenceAnimalsCarrier ProteinsCell Line, TumorCell ProliferationCluster AnalysisDrosophilaGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMediator ComplexProstatic NeoplasmsProtein BindingProtein Kinase InhibitorsCarrier ProteinsHIPK2 protein, humanMED19 protein, humanMediator ComplexProtein Kinase InhibitorsProtein Serine-Threonine KinasesReceptors, Androgen

Identifiers

PMID23403032
PMCPMC3613576
OpenAlexW2153812043

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.