Regulatory interplay between miR-21, JAG1 and 17beta-estradiol (E2) in breast cancer cells

Biochem Biophys Res Commun. 2012 Jun 29;423(2):234-9. doi: 10.1016/j.bbrc.2012.05.074. Epub 2012 May 19.


Overexpression of the oncomir miR-21 is associated with many cancers, including breast cancer. Elevated levels of Jagged-1 (JAG1), a predicted miR-21 target, are implicated in estrogen receptor negative (ER-) breast cancer. We demonstrate (by ablation of the miR-21 binding site in the JAG1 3'UTR) that miR-21 directly targets and represses JAG1 levels in MCF-7 (ER+) breast cancer cells. MiR-21 targeting of JAG1 in MDA-MB-231 (ER-) breast cancer cells is dependent on miR-21 dosage (levels). In both cell lines, miR-21 and JAG1 expression levels were negatively correlated due to their regulatory relationship. In addition, 17beta-estradiol (E2) increases JAG1 levels by limiting (via downregulating miR-21 levels) the repressive effects of miR-21 on the JAG1 3'UTR. Our results reveal a regulatory interplay between miR-21, JAG1 and E2 that is important for advancing understanding of how the oncogenic potential of miR-21 and JAG1 manifests in different sub-types of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Breast Neoplasms / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Cell Line, Tumor
  • Down-Regulation
  • Estradiol / metabolism*
  • Estradiol / pharmacology
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Jagged-1 Protein
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • Serrate-Jagged Proteins


  • 3' Untranslated Regions
  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • MIRN21 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Serrate-Jagged Proteins
  • Estradiol