Progestin regulated miRNAs that mediate progesterone receptor action in breast cancer

Mol Cell Endocrinol. 2012 May 15;355(1):15-24. doi: 10.1016/j.mce.2011.12.020. Epub 2012 Jan 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Genes, Reporter
  • Humans
  • Luciferases
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microarray Analysis
  • Progestins / metabolism
  • Progestins / pharmacology*
  • Promoter Regions, Genetic
  • Protein Biosynthesis / drug effects
  • Receptors, Progesterone / metabolism*
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Transcription, Genetic / drug effects
  • Transfection


  • 3' Untranslated Regions
  • ATP1B1 protein, human
  • MicroRNAs
  • Progestins
  • Receptors, Progesterone
  • Luciferases
  • Sodium-Potassium-Exchanging ATPase