The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop.
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.
Ramasamy
Selvi
S
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Duraisamy
Sekhar
S
Barbashov
Sergei
S
Kawano
Takeshi
T
Kharbanda
Surender
S
Kufe
Donald
D
D000595:Amino Acid Sequence; D000818:Animals; D001216:Asparagine / Q000378:metabolism; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D037502:Galectin 3; C060192:MUC1 protein, human; D035683:MicroRNAs; D018396:Mucin-1; D015513:Oncogene Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D001216:Asparagine; D066246:ErbB Receptors