The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop

Mol Cell. 2007 Sep 21;27(6):992-1004. doi: 10.1016/j.molcel.2007.07.031.


The MUC1 heterodimeric transmembrane glycoprotein is aberrantly overexpressed by diverse human carcinomas. Galectin-3 is a beta-galactoside binding protein that has also been associated with the development of human cancers. The present results demonstrate that MUC1 induces galectin-3 expression by a posttranscriptional mechanism. We show that the MUC1 C-terminal subunit is glycosylated on Asn-36 and that this modification is necessary for upregulation of galectin-3. N-glycosylated MUC1-C increases galectin-3 mRNA levels by suppressing expression of the microRNA miR-322 and thereby stabilizing galectin-3 transcripts. The results show that, in turn, galectin-3 binds to MUC1-C at the glycosylated Asn-36 site. The significance of the MUC1-C-galectin-3 interaction is supported by the demonstration that galectin-3 forms a bridge between MUC1 and the epidermal growth factor receptor (EGFR) and that galectin-3 is essential for EGF-mediated interactions between MUC1 and EGFR. These findings indicate that MUC1 and galectin-3 function as part of a miR-322-dependent regulatory loop.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Asparagine / metabolism
  • CHO Cells
  • Cell Line, Tumor
  • Cricetinae
  • Cricetulus
  • Down-Regulation / genetics
  • ErbB Receptors / metabolism
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Glycosylation
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Mucin-1 / chemistry
  • Mucin-1 / metabolism*
  • Oncogene Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • RNA Stability
  • RNA, Messenger / metabolism
  • Up-Regulation / genetics


  • Galectin 3
  • MUC1 protein, human
  • MicroRNAs
  • Mucin-1
  • Oncogene Proteins
  • Protein Subunits
  • RNA, Messenger
  • Asparagine
  • ErbB Receptors