Evidence map›Paper›PMID 22442719›Full record

Trial reportPloS one2012

Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM.

Dejuan Kong, Elisabeth Heath, Wei Chen, Michael L Cher, Isaac Powell, Lance Heilbrun, Yiwei Li, Shadan Ali, Seema Sethi, Oudai Hassan and 6 more

Open access · goldAbstract readClinical Trial, Phase II
In one paragraph

Trial report in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 1 pooled it
10.0field-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

111 citing papers in PubMed, 1 synthesis or guideline pooled it, 214 citations in OpenAlex.

  1. Low expression of let-7 predicts poor prognosis in patients with multiple cancers: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    Pooled it
  2. Epigenetic regulation of EZH2 by ncRNAs: mechanisms and oncogenic implications.Naunyn-Schmiedeberg's archives of pharmacology · 2026
    Review
  3. Review
  4. Article
  5. Prostate cancer stem cells and their targeted therapies.Frontiers in cell and developmental biology · 2024
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. microRNA-205 in prostate cancer: Overview to clinical translation.Biochimica et biophysica acta. Reviews on cancer · 2022
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article

51 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

16 authors at 4 institutions in 1 country.

Dejuan KongDepartment of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
Elisabeth Heath
Wei Chen
Michael L Cher
Isaac Powell
Lance Heilbrun
Yiwei Li
Shadan Ali
Seema Sethi
Oudai Hassan
Clara Hwang
Nilesh Gupta
Dhananjay Chitale
Wael A Sakr
Mani Menon
Fazlul H Sarkar
Wayne State University · USThe Barbara Ann Karmanos Cancer Institute · USMichigan United · USHenry Ford Health System · US

Funding

Novel Targets of Indoles in Prostate CancerR01CA108535 · NCI · WAYNE STATE UNIVERSITY · PI SARKAR, FAZLUL H. · 2004 to 2014
$2.7M
Molecular Mechanism of Genistein (Isoflavone) in Prostate CancerR01CA083695 · NCI · WAYNE STATE UNIVERSITY · PI SARKAR, FAZLUL H. · 2001 to 2011
$2.3M
Mechanistic Role of miRNAs and Their Targets in Prostate Cancer AggressivenessR01CA164318 · NCI · WAYNE STATE UNIVERSITY · PI SARKAR, FAZLUL H. · 2012 to 2015
$1.3M
NCI NIH HHS 5R01CA083695-08NCI NIH HHS 5R01CA108535-06NCI NIH HHS R01 CA083695NCI NIH HHS R01 CA108535NCI NIH HHS R01 CA164318
6 · The paper itself

Abstract

The emergence of castrate-resistant prostate cancer (CRPC) contributes to the high mortality of patients diagnosed with prostate cancer (PCa), which in part could be attributed to the existence and the emergence of cancer stem cells (CSCs). Recent studies have shown that deregulated expression of microRNAs (miRNAs) contributes to the initiation and progression of PCa. Among several known miRNAs, let-7 family appears to play a key role in the recurrence and progression of PCa by regulating CSCs; however, the mechanism by which let-7 family contributes to PCa aggressiveness is unclear. Enhancer of Zeste homolog 2 (EZH2), a putative target of let-7 family, was demonstrated to control stem cell function. In this study, we found loss of let-7 family with corresponding over-expression of EZH2 in human PCa tissue specimens, especially in higher Gleason grade tumors. Overexpression of let-7 by transfection of let-7 precursors decreased EZH2 expression and repressed clonogenic ability and sphere-forming capacity of PCa cells, which was consistent with inhibition of EZH2 3'UTR luciferase activity. We also found that the treatment of PCa cells with BR-DIM (formulated DIM: 3,3'-diindolylmethane by Bio Response, Boulder, CO, abbreviated as BR-DIM) up-regulated let-7 and down-regulated EZH2 expression, consistent with inhibition of self-renewal and clonogenic capacity. Moreover, BR-DIM intervention in our on-going phase II clinical trial in patients prior to radical prostatectomy showed upregulation of let-7 consistent with down-regulation of EZH2 expression in PCa tissue specimens after BR-DIM intervention. These results suggest that the loss of let-7 mediated increased expression of EZH2 contributes to PCa aggressiveness, which could be attenuated by BR-DIM treatment, and thus BR-DIM is likely to have clinical impact.

Indexed as

AgedAntineoplastic AgentsCell Line, TumorDNA-Binding ProteinsEnhancer of Zeste Homolog 2 ProteinGene Expression Regulation, NeoplasticHumansIndolesMaleMicroRNAsMiddle AgedNeoplasm ProteinsNeoplastic Stem CellsPolycomb Repressive Complex 2Prostatic NeoplasmsRNA, Neoplasm1,1-bis(3'-indolyl)methaneAntineoplastic AgentsDNA-Binding ProteinsEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanIndolesMicroRNAsmirnlet7 microRNA, humanNeoplasm ProteinsPolycomb Repressive Complex 2RNA, NeoplasmTranscription Factors

Identifiers

PMID22442719
PMCPMC3307758
OpenAlexW1973752700

What OpenQuestion holds

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LicenceCC BY
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.