Evidence map›Paper›PMID 19264808›Full record

ArticleNucleic acids research2009

Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells.

Nalinie S Wickramasinghe, Tissa T Manavalan, Susan M Dougherty, Krista A Riggs, Yong Li, Carolyn M Klinge

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 1 pooled it
12.7field-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

182 citing papers in PubMed, 1 synthesis or guideline pooled it, 390 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. MicroRNA-21 is a potential therapeutic agent targetingMolecular therapy. Nucleic acids · 2025
    Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Trials and Tribulations of MicroRNA Therapeutics.International journal of molecular sciences · 2024
    Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

122 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

6 authors at 1 institution in 1 country.

Nalinie S WickramasingheDepartment of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Tissa T Manavalan
Susan M Dougherty
Krista A Riggs
Yong Li
Carolyn M Klinge
University of Louisville · US

Funding

UOFL ENVIRONMENTAL HEALTH SCIENCES TRAINING PROGRAMT32ES011564 · NIEHS · UNIVERSITY OF LOUISVILLE · PI David W Hein, John Pierce Wise · 2004 to 2026
$7.1M
Regulation of miRNA expression in breast cancer cellsR21CA124811 · NCI · UNIVERSITY OF LOUISVILLE · PI KLINGE, CAROLYN M. · 2007 to 2009
$342k
Intramural NIH HHSNCI NIH HHS R21 CA124811NIEHS NIH HHS T32 ES011564
6 · The paper itself

Abstract

Select changes in microRNA (miRNA) expression correlate with estrogen receptor alpha (ER alpha) expression in breast tumors. miR-21 is higher in ER alpha positive than negative tumors, but no one has examined how estradiol (E(2)) regulates miR-21 in breast cancer cells. Here we report that E(2) inhibits miR-21 expression in MCF-7 human breast cancer cells. The E(2)-induced reduction in miR-21 was inhibited by 4-hydroxytamoxifen (4-OHT), ICI 182 780 (Faslodex), and siRNA ER alpha indicating that the suppression is ER alpha-mediated. ER alpha and ER beta agonists PPT and DPN inhibited and 4-OHT increased miR-21 expression. E(2) increased luciferase activity from reporters containing the miR-21 recognition elements from the 3'-UTRs of miR-21 target genes, corroborating that E(2) represses miR-21 expression resulting in a loss of target gene suppression. The E(2)-mediated decrease in miR-21 correlated with increased protein expression of endogenous miR-21-targets Pdcd4, PTEN and Bcl-2. siRNA knockdown of ER alpha blocked the E(2)-induced increase in Pdcd4, PTEN and Bcl-2. Transfection of MCF-7 cells with antisense (AS) to miR-21 mimicked the E(2)-induced increase in Pdcd4, PTEN and Bcl-2. These results are the first to demonstrate that E(2) represses the expression of an oncogenic miRNA, miR-21, by activating estrogen receptor in MCF-7 cells.

Indexed as

Gene Expression Regulation, Neoplastic3' Untranslated RegionsApoptosis Regulatory ProteinsBreast NeoplasmsCell Line, TumorCycloheximideDactinomycinDown-RegulationEstradiolEstrogen AntagonistsEstrogen Receptor alphaEstrogen Receptor betaFemaleFulvestrantGenes, ReporterHumans3' Untranslated RegionsafimoxifeneApoptosis Regulatory ProteinsCycloheximideDactinomycinEstradiolEstrogen AntagonistsEstrogen Receptor alphaEstrogen Receptor betaFulvestrantMicroRNAsMIRN21 microRNA, humanNucleic Acid Synthesis InhibitorsPDCD4 protein, humanProtein Synthesis Inhibitorsras GTPase-Activating ProteinsRNA, AntisenseRNA-Binding ProteinsTamoxifen

Identifiers

PMID19264808
PMCPMC2677875
OpenAlexW2130018512

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.