Fig. 2

Glycan synthesis and epigenetic miRNA-regulation of the glycosylation machinery in the tumor microenvironment. (Top panel) MiRNA regulation in the glycan precursor synthesis (sugar/nucleotide sugar transport and monosaccharide synthesis). Sugar transporters transport different types of extracellular sugars into cells (dashed lines), and the sugars are further converted into nucleotide sugars (solid lines). The filled black circle indicated metabolites leading to nucleotide sugars, and all the other graphical symbols match those in Symbol Nomenclature for Glycans (SNFG) (https://www.ncbi.nlm.nih.gov/glycans/snfg.html). The nucleotide sugar synthesis pathway is replotted from [96]. (Bottom panel) MiRNA regulation in the N-linked glycan synthesis. The monosaccharides will be transported (dashed lines) to ER or Golgi, in which a variety of glycosyltransferases are responsible for a series of reactions (e.g., precursor synthesis, core branching, and maturation; indicated in the bottom panel) to synthesize complex glycans. All the miRNA regulations in the glycosylation machinery are indicated by red colors, in which the miRNAs were experimentally validated to target these glycosyltransferases (see details in the main text). All the enzymes or transporters are indicated by their gene symbols (blue colors)