Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines

Anticancer Res. 2018 Dec;38(12):6691-6697. doi: 10.21873/anticanres.13037.

Abstract

Background/aim: The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.

Materials and methods: Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.

Results: Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level. Of interest, basal levels of O-GlcNAc in resting HL-60 and HT-29 cells were significantly higher than those in cells differentiated into neutrophilic or enterocytic lineages, respectively.

Conclusion: O-GlcNAc-mediated signaling pathways may be involved in regulating the expression of only a limited number of galectin genes. Additional O-GlcNAc-dependent mechanisms may work at the protein level (galectin secretion and intracellular localization) and warrant further investigation.

Keywords: Cancer cells; O-GlcNAc; cell biology; galectins; glycobiology.

MeSH terms

  • Blood Proteins
  • Enzyme Inhibitors / pharmacology
  • Galectin 3 / genetics
  • Galectin 3 / metabolism
  • Galectins / genetics*
  • Galectins / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycosylation / drug effects
  • HL-60 Cells
  • HT29 Cells
  • Humans
  • MCF-7 Cells
  • N-Acetylglucosaminyltransferases / antagonists & inhibitors
  • N-Acetylglucosaminyltransferases / metabolism*
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Transcriptome / drug effects
  • beta-N-Acetylhexosaminidases / antagonists & inhibitors
  • beta-N-Acetylhexosaminidases / metabolism*

Substances

  • Blood Proteins
  • Enzyme Inhibitors
  • Galectin 3
  • Galectins
  • LGALS12 protein, human
  • LGALS3 protein, human
  • N-Acetylglucosaminyltransferases
  • O-GlcNAc transferase
  • hexosaminidase C
  • beta-N-Acetylhexosaminidases