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

Abstract

Summary 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. 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.

Scan_Tcga Tools for Integrated Epigenomic and Transcriptomic Analysis of Tumor Subgroups

“…We observed that a group of miRNAs were consistently expressed either at a high level (e.g., let7a/b, miR-21 and miR-30d, Figure 6) or a low level (e.g., miR-34b, miR-26a, miR-137, miR-18b). These results are consistent with previous reports of deregulation of future science group Methodology Chatterjee, Stockwell, Rodger, Parry & Eccles these miRNAs in melanoma [43][44][45][46][47][48]. Furthermore, a group of miRNA showed distinct expression profiles between primary and melanoma patients.…”

Melanoma and Associated MicroRNAs

“…Moreover, some diagnostic miRNAs can be used in therapy. For instance, in previous studies, miR-155, which is downregulated in melanoma, was injected in melanoma cell lines to increase its expression (1,21,22). Similar procedures can be executed for miR-193b as a practical therapeutic option (1).…”

“…This gene modifies the cell surface of melanoma cells and affects cellular adherence; metastasis occurs due to discontinuity of cancerous cells. Therefore, miR-30b and miR-30 are accountable for metastasis in melanoma (1,21,22).…”

Signaling Pathways Altered During the Metastatic Progression of Melanoma

“…In addition to the increased metastatic potential, the upregulation of these miRNAs correlates with shorter time to recurrence and reduced overall survival. Overexpression of miR-30b/30d promotes melanoma metastasis by modifying the glycosylation pattern of transmembrane proteins, more specifically by directly repressing GalNAc transferase GALNT7, which culminates in pro-invasive and immunosuppressive effects [120].…”