Table 1 Exosomes emerge as an intercellular shuttle between cancer cells and CAAs

miR-144 from cancer cells is able to target the MAP3K8 gene and reduce the phosphorylation level of ERK1/2, which leads to a decrease in the phosphorylation level of PPARγ S273 in adipocytes, ultimately leading to an increase in the expression of UCP1.

[66]

miR-126, derived from breast cancer cells, can target the IRS-1 gene to downregulate the expression of glut4 in adipocytes, which leads to a decrease in glucose uptake of adipocytes. And then AMPK is activated and protein levels of HIF-1α and MCT4 are increased, resulting in an increase of glycolysis and the secretion of metabolites, such as lactic acid and pyruvic acid.

[66]

miR-155 promotes beige/brown differentiation and remodels metabolism in adipocytes by downregulating the PPARγ expression.

[114]

miR-122 suppresses the uptake of glucose in premetastatic niche cells by decreasing the glycolytic enzyme pyruvate kinase, thereby facilitating disease progression.

[115]

miR-105 activates MYC signaling in CAFs and CAAs to induce a metabolic program. And miR-105-reprogrammed CAFs enhance the metabolism of glucose and glutamine, fueling neighboring cancer cells in sufficient nutrient conditions, while these CAFs convert metabolic wastes such as lactic acid and ammonium into energy-rich metabolites in situations of nutrient deficiency.

[116,117,118]

Exosomes released from gastric cancer cells deliver ciRS-133 to pre-adipocytes, modulating the differentiation of pre-adipocytes to brown-like adipocytes through activating PRDM16 and inhibiting miRNA-133.

[119]

miR-21 is transported from CAAs to cancer cells, inhibiting the apoptosis of ovarian cancer cells and producing chemotherapy resistance by combining with its direct new target APAF1.

[125,126,127]

miR-210 released from adipose-derived stem cells promoted the proliferation, invasion and migration of endothelial cells by targeting RUNX3, suggesting that exosomal miR-210 may mediate tumor angiogenesis.

[130]