Figure 4.

Synoptic model depicting exosomal miR-21 traffic in the melanocyte and melanoma microenvironment. Cosmic and UV irradiation induce the release of keratinocyte-and fibroblast-derived miR-21-enriched exosomes, which may increase melanocyte miR-21 levels. Adipose tissue-derived exosomal miR-21 in obesity may further increase melanocyte miR-21 levels. Melanocyte miR-21 may be further enhanced by circulatory exosomes generated by a Western diet, milk consumption, smoking, inflammation, tumors and aging. Increased miR-21 levels in melanoma-associated macrophages and skin resident CD8+ memory T-cells further promote MM progression.