MiR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis

ABSTRACT: To 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 simultaneously. We performed a microRNA analysis of human melanoma, an aggressively invasive cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic potential of primary tumors, 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 point to a key role of miR-30b/30d and GalNAc transferases in metastasis, by simultaneously promoting cellular invasion and immune suppression. MicroRNAs are emerging as key contributors to tumor metastasis because of their ability to regulate multiple targets, and thereby alter several functions, simultaneously. We found a miRNA cluster that promotes metastasis by concurrently enhancing invasive capabilities of melanoma cells and suppressing immune surveillance mechanisms, allowing the tumor cells to migrate and invade foreign tissue. Both these effects of miR-30b/30d are mediated by direct suppression of GalNAc transferases. Aberrant glycosylation has previously been connected to tumor progression, but the underlying molecular mechanisms and their impact on specific cellular pathways are poorly understood. Our work places the control of glycosylation as a novel molecular link between tumor cell migration and immune evasion, two processes that act synergistically during metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE27718 | GEO | 2011/03/08

SECONDARY ACCESSION(S): PRJNA138087

REPOSITORIES: GEO