Scientists from New York University and the University of Texas at Austin report that carbohydrates can serve as identifiers for cancer cells. They say their study (“Mapping posttranscriptional regulation of the human glycome uncovers microRNA defining the glycocode”), which appears in the Proceedings of the National Academy of Sciences, shows how these molecules may serve as signals for cancer and explain what’s going on inside these cells.
“[Carbohydrates] are potentially good markers for disease,” said Lara Mahal, Ph.D., an associate professor in NYU’s department of chemistry and the paper’s corresponding author. “Our study reveals how cancer cells produce certain ‘carbohydrate signatures’ that we can now identify.”
Carbohydrates, or glycans, are complex cell-surface molecules that control multiple aspects of cell biology, including cancer metastasis. But less understood is the link between categories of cells and corresponding carbohydrate structures. That is, what do certain carbohydrates on a cell’s surfaces tell us about its characteristics and inner workings or, more succinctly, how do you read a code backwards?
In the PNAS study, the researchers examined the role of microRNA, noncoding RNA that are regulators of the genome. Specific miRNAs—such as miR-200—play a role in controlling tumor growth. Using microarray technology developed by NYU’s Dr. Mahal, the team examined cancer cells in an effort to see how they generated a carbohydrate signature. Specifically, they mapped how miRNA controls carbohydrate signatures.
In their analysis, the researchers could see that miRNA molecules serve as major regulators of the cell’s surface-level carbohydrates—a discovery that showed, for the first time, that miRNA play a significant regulatory role in this part of the cell, also known as the glycome. Moreover, they could see which regulatory process was linked to specific carbohydrates.
“By using our glycomic analysis platform, lectin microarrays, we identify glycosylation signatures in the NCI-60 cell panel that point to the glycome as a direct output of genomic information flow. Integrating our glycomic dataset with miRNA data, we map miRNA regulators onto genes in glycan biosynthetic pathways (glycogenes) that generate the observed glycan structures,” wrote the investigators. “We validate three of these predicted miRNA/glycogene regulatory networks: high mannose, fucose, and terminal β-GalNAc, identifying miRNA regulation that would not have been observed by traditional bioinformatic methods. Overall, our work reveals critical nodes in the global glycosylation network accessible to miRNA regulation, providing a bridge between miRNA-mediated control of cell phenotype and the glycome.”
Carbohydrates aren't just providing the information on the type of cell they came from, but also by which process they were created, according to Dr. Mahal. “Our results showed that there are regulatory networks of miRNAs and that they are associated with specific carbohydrate codes,” she said.