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.

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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