Fig. 11

Dairy milk exosomes and prostate tumorigenesis. Milk exosome-derived miR-148a, miR-29b and miR-21 suppress DNA methyltransferase 1 (DNMT1), a critical step in prostate cancer (PCa) epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) formation. miR-148a-mediated suppression of DNMT1 enhances the expression of fat mass and obesity-associated gene (FTO), which increases the expression of CCAAT enhancer element binding protein-β (C/EBPβ), a potential mechanism increasing the expression of α-methylacyl-CoA racemase (AMACR). DNMT1 is also a negative regulator of androgen receptor (AR) signaling. Milk exosomes provide miR-155 and transforming growth factor-β (TGFβ), which further induces miR-155, which inhibits suppressor of cytokine signaling 1 (SOCS1), a pivotal inhibitor of EMT. Milk-derived exosomal miR-21 increases the pool of a key oncogenic miR, which suppresses key checkpoint regulators of cell cycle progression and apoptotic signaling including phosphatase and tensin homolog (PTEN), cyclin-dependent kinase inhibitor 1C (CDKN1C, p57kip2), programmed cell death 4 (PDCD4), myristolylated alanine-rich protein kinase C substrate (MARCKS) and others