Evidence map›Paper›PMID 34127806›Full record

ArticleCell death and differentiation2021

Targeting androgen receptor (AR) with antiandrogen Enzalutamide increases prostate cancer cell invasion yet decreases bladder cancer cell invasion via differentially altering the AR/circRNA-ARC1/miR-125b-2-3p or miR-4736/PPARγ/MMP-9 signals.

Gang Deng, Ronghao Wang, Yin Sun, Chi-Ping Huang, Shuyuan Yeh, Bosen You, Changyong Feng, Gonghui Li, Shenglin Ma, Chawnshang Chang

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 3 pooled it
4.1field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. The Emerging Role of Circular RNAs in Prostate Cancer: A Systematic Review.Frontiers in cell and developmental biology · 2021
    Pooled it
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
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  11. Review
  12. Review
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  14. Article
  15. Review
  16. Article
  17. GαCancers · 2024
    Article
  18. The androgen receptor in bladder cancer.Nature reviews. Urology · 2023
    Review
  19. Article
  20. Review
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

10 authors at 3 institutions in 3 countries.

Gang Deng *Department of Urology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ronghao Wang *George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
Yin Sun *George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
Chi-Ping Huang *Department of Urology, China Medical University/Hospital, Taichung, Taiwan.ORCID http://orcid.org/0000-0003-1429-1366
Shuyuan YehGeorge Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.ORCID http://orcid.org/0000-0002-5329-2321
Bosen YouGeorge Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
Changyong FengDepartment of Biostatistics, University of Rochester Medical Center, Rochester, NY, USA.
Gonghui LiGeorge Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
Shenglin MaDepartment of Urology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China. mashenglin@medmail.com.cn.
Chawnshang ChangGeorge Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. chang@urmc.rochester.edu.ORCID http://orcid.org/0000-0001-8510-3516
University of Rochester Medical Center · USChina Medical University · TWHangzhou First People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Androgen-deprivation therapy (ADT) via targeting androgens/androgen receptor (AR) signals may suppress cell proliferation in both prostate cancer (PCa) and bladder cancer (BCa), yet its impact on the cell invasion of these two urological cancers remains unclear. Here we found targeting androgens/AR with either the recently developed antiandrogen Enzalutamide (Enz) or AR-shRNAs led to increase PCa cell invasion, yet decrease BCa cell invasion. Mechanistic dissection revealed that suppressing androgens/AR signals could result in differential alterations of the selective circular RNAs (circRNAs) as a result of differential endogenous AR transcription. A negative autoregulation in PCa, yet a positive autoregulation in BCa, as a result of differential binding of AR to different androgen-response elements (AREs) and a discriminating histone H3K4 methylation, likely contributes to this outcome between these two urological tumors. Further mechanistic studies indicated that AR-encoded circRNA-ARC1 might sponge/alter the availability of the miRNAs miR-125b-2-3p and/or miR-4736, to impact the metastasis-related PPARγ/MMP-9 signals to alter the PCa vs. BCa cell invasion. The preclinical study using the in vivo mouse model confirms in vitro cell lines data, showing that Enz treatment could increase PCa metastasis, which can be suppressed after suppressing circRNA-ARC1 with sh-circRNA-ARC1. Together, these in vitro/in vivo results demonstrate that antiandrogen therapy with Enz via targeting AR may lead to either increase PCa cell invasion or decrease BCa cell invasion. Targeting these newly identified AR/circRNA-ARC1/miR-125b-2-3p and/or miR-4736/PPARγ/MMP-9 signals may help in the development of new therapies to better suppress the Enz-altered PCa vs. BCa metastasis.

Indexed as

Androgen AntagonistsAnimalsBenzamidesCell Line, TumorCell ProliferationHumansMaleMatrix Metalloproteinase 9MiceMice, NudeMicroRNAsNeoplasm InvasivenessNitrilesPhenylthiohydantoinPPAR gammaProstatic NeoplasmsAndrogen AntagonistsAR protein, humanBenzamidesenzalutamideMatrix Metalloproteinase 9MicroRNAsMIRN125 microRNA, humanMMP9 protein, humanNitrilesPhenylthiohydantoinPPAR gammaReceptors, AndrogenRNA, Circular

Identifiers

PMID34127806
PMCPMC8257744
OpenAlexW3169072539

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.