miR-182, of the miR-183 cluster family, is packaged in exosomes and is detected in human exosomes from serum, breast cells and prostate cells

Abstract

Members of the microRNA (miR)-183 family are expressed at high levels in the majority of cancer types, including breast and prostate, and are considered 'oncomiRs'. The purpose of the present study was to investigate the role of exosomes in cell-to-cell transfer of the miR‑183 family, which includes miRs‑96, ‑182 and ‑183. Despite highly detectable levels of these three miRs within prostate and breast cells in vitro, only miR‑182 was detectable in exosomes isolated from cell culture supernatant. Similar to the in vitro results, miR‑182 was the only miR detected in exosomes isolated from fresh human serum. The packaging of miR‑182 into exosomes was examined in MDA‑MB‑231 (MDA‑182) breast cancer cells with miR‑182 overexpression. Levels of mature miR‑182 increased in exosomes in a dose‑dependent manner compared to intracellular expression. Furthermore, co‑culture of MDA‑182 cells with naïve MDA‑MB‑231 cells resulted in an increase in mature miR‑182 in the naïve cells, which was blocked by a chemical inhibitor of microvesicle formation. In summary, the present study demonstrates that of the miR‑183 family members, miR‑182 is preferentially packaged in exosomes, detectable in exosomes from human sera and may be transferred between cells via a microvesicle-dependent mechanism.