MiRNA proxy approach reveals hidden functions of glycosylation

Tomasz Kurcon, Zhongyin Liu, Anika V. Paradkar, Christopher A. Vaiana, Sujeethraj Koppolu, Praveen Agrawal, Lara K. Mahal

Research output: Contribution to journalArticlepeer-review

Abstract

Glycosylation, the most abundant posttranslational modification, holds an unprecedented capacity for altering biological function. Our ability to harness glycosylation as a means to control biological systems is hampered by our inability to pinpoint the specific glycans and corresponding biosynthetic enzymes underlying a biological process. Herein we identify glycosylation enzymes acting as regulatory elements within a pathway using microRNA (miRNA) as a proxy. Leveraging the target network of the miRNA-200 family (miR-200f), regulators of epithelial-to-mesenchymal transition (EMT), we pinpoint genes encoding multiple promesenchymal glycosylation enzymes (glycogenes). We focus on three enzymes, beta-1,3-glucosyltransferase (B3GLCT), beta-galactoside alpha-2,3-sialyltransferase 5 (ST3GAL5), and (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl-1,3)-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5), encoding glycans that are difficult to analyze by traditional methods. Silencing these glycogenes phenocopied the effect of miR-200f, inducing mesenchymal-to-epithelial transition. In addition, all three are up-regulated in TGF-β-induced EMT, suggesting tight integration within the EMT-signaling network. Our work indicates that miRNA can act as a relatively simple proxy to decrypt which glycogenes, including those encoding difficult-toanalyze structures (e.g., proteoglycans, glycolipids), are functionally important in a biological pathway, setting the stage for the rapid identification of glycosylation enzymes driving disease states.

Original languageEnglish (US)
Pages (from-to)7327-7332
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number23
DOIs
StatePublished - Jun 9 2015

Keywords

  • Epithelial to mesenchymal transition
  • Glycan regulation
  • Glycomics
  • MiR-200
  • TGF-beta

ASJC Scopus subject areas

  • General

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