Evidence map›Paper›PMID 24778216›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation.

Chen-Lin Hsieh, Teng Fei, Yiwen Chen, Tiantian Li, Yanfei Gao, Xiaodong Wang, Tong Sun, Christopher J Sweeney, Gwo-Shu Mary Lee, Shaoyong Chen and 4 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers.

0numbers the graph read from it
0cells of the map it votes in
257citing papers in PubMed
13.4field-weighted citation impact, top 1% 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

257 citing papers in PubMed, 401 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Direct roles of long non-coding RNAs in transcription activation.Nature structural & molecular biology · 2026
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Enhancer regulation in cancer: from epigenetics to mArchives of pharmacal research · 2025
    Review
  20. Review

197 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

14 authors at 3 institutions in 1 country.

Chen-Lin HsiehDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115;
Teng FeiDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115;Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215;
Yiwen ChenCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215;Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115; and.
Tiantian LiDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115;
Yanfei GaoHematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
Xiaodong WangDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115;
Tong SunDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115;
Christopher J SweeneyDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115;
Gwo-Shu Mary LeeDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115;
Shaoyong ChenHematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
Steven P BalkHematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
Xiaole Shirley LiuCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215;Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115; and.
Myles BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115;Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215;
Philip W KantoffDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115; philip_kantoff@dfci.harvard.edu.
Harvard University · USDana-Farber Cancer Institute · USBeth Israel Deaconess Medical Center · US

Funding

Tumor and Circulating Markers as Links Between Obesity and Lethal Prostate CanceP50CA090381 · NCI · DANA-FARBER CANCER INSTITUTE · PI LODA, MASSIMO · 2002 to 2017
$36.2M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI EVA COREY · 2013 to 2026
$25.0M
An integrated approach to dissect the functional network of large non-coding RNAK99CA175290 · NCI · DANA-FARBER CANCER INST · PI CHEN, YIWEN · 2013 to 2014
$225k
NCI NIH HHS K99 CA175290NCI NIH HHS P01 CA163227NCI NIH HHS P50 CA090381NCI NIH HHS P50CA090381
6 · The paper itself

Abstract

The androgen receptor (AR) is a key factor that regulates the behavior and fate of prostate cancer cells. The AR-regulated network is activated when AR binds enhancer elements and modulates specific enhancer-promoter looping. Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e. Here, we demonstrate that KLK3e facilitates the spatial interaction of the KLK3 enhancer and the KLK2 promoter and enhances long-distance KLK2 transcriptional activation. KLK3e carries the core enhancer element derived from the androgen response element III (ARE III), which is required for the interaction of AR and Mediator 1 (Med1). Furthermore, we show that KLK3e processes RNA-dependent enhancer activity depending on the integrity of core enhancer elements. The transcription of KLK3e was detectable and its expression is significantly correlated with KLK3 (R(2) = 0.6213, P < 5 × 10(-11)) and KLK2 (R(2) = 0.5893, P < 5 × 10(-10)) in human prostate tissues. Interestingly, RNAi silencing of KLK3e resulted in a modest negative effect on prostate cancer cell proliferation. Accordingly, we report that an androgen-induced eRNA scaffolds the AR-associated protein complex that modulates chromosomal architecture and selectively enhances AR-dependent gene expression.

Indexed as

Enhancer Elements, GeneticGene Expression Regulation, NeoplasticAnimalsCell Line, TumorChlorocebus aethiopsCOS CellsGene SilencingHumansKallikreinsMaleMediator Complex Subunit 1Promoter Regions, GeneticProstateProstate-Specific AntigenProstatic NeoplasmsReceptors, AndrogenAR protein, humanKallikreinsKLK3 protein, humanMED1 protein, humanMediator Complex Subunit 1Prostate-Specific AntigenReceptors, AndrogenTissue Kallikreinschromosomal loopingKLK3e/AR/Med1 complex

Identifiers

PMID24778216
PMCPMC4034202
OpenAlexW1995226230

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.