MicroRNA define the glycocode: identification of critical glycogenes that shape the cell (788.6)

Abstract

Cell surface glycans create an intricate source of biological information which is dynamically altered by cells in developmental processes and used by pathogens during host invasion. Mapping of the glycocode and identification of critical glycan altering enzymes in biological processes is confounded by the complexity and redundancy of glycan biosynthetic machinery. Recently, we integrated microRNA (miRNA) expression data with our glycomics analysis for the NCI‐60 cancer cell line panel, and showed that miRNA act as a major regulator of the human glycome by targeting critical nodes within the glycan biosynthesis pathway. Among others, our analysis revealed a strong association of fucose signature and miRNA‐200 family (miR‐200f), known regulators of epithelial to mesenchymal transition (EMT) a process during which miR‐200f is downregulated. Within the NCI‐60, expression pattern of miR‐200f maps onto fucose signature: both are high in epithelial and low in mesenchymal cells, indicating that fucose might be a marker of epithelial/mesenchymal cell state. In line with our findings we utilize miRNA target prediction software and identify a secreted α‐fucosidase (FUCA2) and O‐linked fucose β‐1,3‐glucosyltransferase (B3GALTL) as most common predicted targets. Both enzymes have the potential to reduce availability of terminal fucose and are downregulated by miRNA‐200f. We show that B3GALTL has a direct role in EMT as B3GALTL knockout induced a change in morphology from mesenchymal to epithelial in mesenchymal breast (MB‐231) and melanoma (M14) cell lines. Taken together our data validates miRNA based mapping of the glycome and identifies B3GALTL as an important regulator of EMT.Grant Funding Source: Sponsored by NIH