Uncovering regulatory nodes in miRNA‐mediated regulation of glycome (608.7)

Abstract

Glycan biosynthesis is a complex and highly non‐linear process requiring a large number of diverse proteins (glycosyltransferases, glycosidases and sugar nucleotide transporters) to act in accord. An increasing number of recent reports, including previous work from our lab, suggest a possible role of microRNAs (miRNAs), small non‐coding RNA that complement to the 3’ or 5’ untranslated region (UTR) of mRNA to attenuate translation, in the regulation of overall glycan expression (glycome) via post‐transcriptional regulation of glycan related gene expression. In this work, we hoped to identify the key regulatory nodes in glycan biosynthetic pathways that might help in the deconvolution of glycomic signals. Adding a more functional approach, we further generated a condition‐driven model with Ovarian Cancer Metastasis (OCM) to identify any glycosylation patterns. Using miRNA prediction data from microrna.org and 3’ UTR lengths from ENCODE project, a metric, called Hit Density (HD), was calculated for each of the glycogenes that incorporate factors contributing to the miRNA regulation of genes. We identified key regulatory nodes in the glycan biosynthetic pathways at the miRNA regulatory level, and show that the glycogenes are not redundant. We also show that orchestration of several events of the glycome can be regulated by miRNA that are predicted to target multiple glycogenes. Finally, bio‐functional mapping of glycan regulatory networks in OCM revealed specific glycosylation patterns, suggesting that glycan regulatory networks in condition‐driven models could impart valuable information.