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Cited by 391

The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.

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

Open access
Wickramasinghe, Nalinie S., Manavalan, Tissa T., Dougherty, Susan M., Riggs, Krista A., Li, Yong, Klinge, Carolyn M.·2009·Nucleic Acids Research

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.

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Metadata

Authors
Wickramasinghe, N. S., Manavalan, T. T., Dougherty, S. M., Riggs, K. A., Li, Y., & Klinge, C. M.
Venue
Nucleic Acids Research
Published
2009-03-05
Volume
37
Issue
8
Pages
2584-2595
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2130018512
Cited by
391
References
80
FWCI
10.59
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. https://app.cochat.ai/papers/10.1093/nar/gkp117
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Wickramasinghe, N. S., Manavalan, T. T., Dougherty, S. M., Riggs, K. A., Li, Y., & Klinge, C. M. (2009). Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. Nucleic Acids Research. https://doi.org/10.1093/nar/gkp117

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