Figure 2.

Proposed models for the role of exosomal miR-21 in CRC development. (a) Fibroblast-derived exosomes have an effect on CRC cells. The internalization of normal fibroblast- (NOF-) derived exosomes into CRC cells leads to an increase of cellular miR-21 and to the activation of phospho-Erk/Akt pathway, leading to oxaliplatin resistance. (b) CRC cells release miR-21-containing exosomes that are able to inhibit endothelial progenitor cell (EPC) IL6R mRNA transcription, leading to a reduced migration, proliferation, and invasion and favoring thrombosis in CRC. (c) Cancer-associated fibroblasts (CAFs) secrete miR-21-overexpressing exosomes which increase liver metastases. Tumor-associated macrophages (TAMs) also release miR-21-containing exosomes that can negatively regulate BRG1 mRNA in CRC cells and lead to an increased migration and proliferation.