miR-30b/30d Regulation of GalNAc Transferases Enhances Invasion and Immunosuppression during Metastasis

SummaryTo metastasize, a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets. We performed a microRNA analysis of human melanoma, a highly invasive cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic potential, shorter time to recurrence, and reduced overall survival. Ectopic expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by directly targeting the GalNAc transferase GALNT7, resulted in increased synthesis of the immunosuppressive cytokine IL-10, and reduced immune cell activation and recruitment. These data support a key role of miR-30b/30d and GalNAc transferases in metastasis, by simultaneously promoting cellular invasion and immunosuppression.

Graphical AbstractFigure optionsDownload high-quality image (127 K)Download as PowerPoint slideHighlights
► miR-30b/d levels associate with advanced stage and poor outcome in melanoma patients
► miR-30d promotes metastasis and immunosuppressive features in vivo
► miR-30d enhances invasion and IL-10 secretion by targeting GalNAc transferases
► miR-30d upregulation leads to GALNT7-dependent alterations in cellular glycosylation