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Updated: May 25, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Progestin regulated miRNAs that mediate progesterone receptor action in breast cancer
Dawn R Cochrane1, Britta M Jacobsen2, Keith D Connaghan3
1Department of Pathology, University of Colorado Denver Anschutz Medical Campus, Denver, USA.
Abstract:
Progesterone receptors (PRs) mediate response to progestins in the normal breast and breast cancer. To determine if liganded PR regulate microRNAs (miRNAs) as a component of their action, we profiled mature miRNA levels following progestin treatment. Indeed, 28 miRNAs are significantly altered by 6h of progestin treatment. Many progestin-responsive genes are putative targets of progestin-regulated miRNAs; for example, progestin treatment decreases miR-29, thereby relieving repression of one of its direct targets, the gene encoding ATPase, Na(+)/K(+) transporting, beta 1 polypeptide (ATP1B1). Thus, liganded PR regulates ATP1B1 through sites in the promoter and the 3'UTR, to achieve maximal tight hormonal regulation of ATP1B1 protein via both transcriptional and translational control. We find that ATP1B1 serves to limit migration and invasion in breast cancer cells. Lastly, we demonstrate that PR itself is regulated by a progestin-upregulated miRNA, miR-513a-5p, providing a novel mechanism for tight control of PR protein expression.
Insights
Progesterone receptors (PRs) regulate microRNAs (miRNAs) in breast cancer. This study reveals that liganded PR controls ATP1B1 expression and limits cancer cell invasion, with PR itself being regulated by miR-513a-5p.
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Progesterone receptors (PRs) mediate progestin responses in normal breast tissue and breast cancer.
- MicroRNAs (miRNAs) are key regulators of gene expression.
Purpose of the Study:
- To investigate whether liganded PRs regulate miRNAs as part of their function.
- To elucidate the role of PR-regulated miRNAs in breast cancer progression.
Main Methods:
- Profiling of mature miRNA levels after progestin treatment.
- Analysis of gene targets for progestin-regulated miRNAs.
- Investigation of ATP1B1 regulation by liganded PR.
- Assessment of ATP1B1's role in breast cancer cell migration and invasion.
- Examination of miRNA-mediated regulation of PR expression.
Main Results:
- Progestin treatment significantly altered 28 miRNAs within 6 hours.
- Progestin treatment decreased miR-29, relieving repression of ATP1B1.
- Liganded PR regulates ATP1B1 via promoter and 3'UTR, controlling both transcription and translation.
- ATP1B1 was found to limit breast cancer cell migration and invasion.
- PR expression is tightly controlled by progestin-upregulated miR-513a-5p.
Conclusions:
- Liganded PRs regulate specific miRNAs, impacting gene expression and cellular functions.
- PR-mediated regulation of ATP1B1 plays a role in suppressing breast cancer cell invasion.
- A novel feedback loop exists where miR-513a-5p regulates PR protein levels, ensuring tight hormonal control.
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