Screening the human miRNA interactome reveals coordinated upregulation in melanoma, adding bidirectional regulation to miRNA networks.

Abstract

Cellular protein expression is coordinated post-transcriptionally by an intricate regulatory network. The current presumption is that miRNA work by repression of functionally related targets within a system. In recent work, upregulation of protein expression via direct interactions of mRNA with miRNA has been found in dividing cells, providing an additional mechanism of regulation. Herein, we demonstrate coordinated upregulation of functionally-coupled proteins by miRNA. We focused on CD98hc, the heavy chain of the amino acid transporter LAT1, and -2,3-sialyltransferases ST3GAL1 and ST3GAL2, which are critical for CD98hc stability in melanoma. Profiling miRNA regulation using our high-throughput miRFluR assay, we identified miRNA that upregulated expression of both CD98hc and either ST3GAL1 or ST3GAL2. These co-upregulating miRNAs were enriched in melanoma datasets associated with transformation and progression. Our findings add co-upregulation by miRNA into miRNA regulatory networks and adds a new bidirectional twist to the impact miRNA have on protein regulation and glycosylation.