Exosomal miRNA: Small Molecules, Big Impact in Colorectal Cancer

Figure 1

Scheme of exosome biogenesis, composition, and major role in TME modification, in the context of CRC. The biogenesis of exosomes involves 4 different steps: (1) the membrane invagination; (2) endosome formation; (3) generation of the exosome precursors, called intraluminal vesicles (ILVs), by inward budding of endosomes (these accumulations of ILVs are termed as multivesicular bodies (MVBs)); and (4) the fusion of MVBs with the plasma membrane release the ILVs in the extracellular space by exocytosis and become exosomes. Composition: exosomes are composed of different types of enzymes and proteins involved in adhesion, intracellular signaling, immunostimulatory molecules, multivesicular body (MVB) formation, and heat shock proteins (HSPs). Exosomes contain nucleic acids, including miRNA, mRNA, DNA, and small noncoding RNA (snRNA and tRNA). In addition to direct interactions between CRC cells and TME, exosomes, especially exosomal miRNAs, play a key role in the cross talk between cells in TME. CRC cells can release exosomes that will modify TME cells and promote tumor growth, metastasis formation, and chemoresistance. Inversely, stromal cells can also release exosomes that influence tumor cell metabolism. Differential expression of miRNAs within exosomes could also be useful in CRC as biomarker for diagnosis and monitoring.