Exosomal miR-21 derived from arsenite-transformed human bronchial epithelial cells promotes cell proliferation associated with arsenite carcinogenesis

Intercellular communications within the cancer microenvironment coordinate the assembly of various cell types. Exosomes are mediators of intercellular communication in immune signaling, tumor promotion, stress responses, and angiogenesis. The present research aimed to determine whether miRNAs secreted from human bronchial epithelial (HBE) cells transformed by 1.0 mu M arsenite are transferred into normal HBE cells and are functionally active in the recipient cells. The results show that miR-21 is involved in exosome-mediated intercellular communication between neoplastic and normal HBE cells. Exosomes derived from transformed HBE cells stimulated proliferation of normal HBE cells, whereas exosomes from miR-21 depleted cells failed to stimulate proliferation. In normal HBE cells, the expression of phosphatase and tensin homolog, a target gene for miR-21, was increased by exosomal miR-21, indicating that exogenous miRNAs, via exosomal transport, function-like endogenous miRNAs. Concordantly, specific reduction of miR-21 content in exosome-producing transformed cells abolished the stimulation of proliferation by exosomes. Collectively, the data indicate that transformed HBE cells release exosomes containing miR-21, stimulating proliferation in neighboring normal HBE cells and supporting the concept that exosomal miRNAs are involved in cell-cell communication during carcinogenesis induced by environmental chemicals.