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.

Exosomal MicroRNAs in Breast Cancer towards Diagnostic and Therapeutic Applications

“…These findings agree with previous studies that showed high levels of these miRNAs in serum or plasma [ 30 , 31 , 32 ]. Analysis of exo-miRNAs from conditioned media of breast cancer cell lines and immortalized breast epithelial cells suggest a differential loading of some miRNAs in exosomes and support the idea that the circulating levels may be higher than in the originating cells [ 25 , 26 , 33 , 34 ]. Such exo-miRNAs could be good candidates for early disease detection.…”

“…Indeed, miR-1246 was among the top miRNAs selectively loaded and secreted in exosomes derived from breast cancer cells (MCF7, Sk-Br-3, MDA-MB-231) relative to immortalized cell lines (MCF10A, IRM90) [ 25 ]. Exo-miR-182 levels were significantly higher than those of exo-miR-96 and exo-miR-183, but these miRNAs were expressed at similar levels in originating breast cancer cells (MCF7, BT474, MDA-MB-231) [ 34 ]. A concern with cell culture studies is that fetal bovine serum (FBS), which is used in most media preparation can contain exo-miRNAs or free-circulating miRNAs, identical in sequence to human miRNAs, and confound result interpretation [ 35 ].…”

Exosomes in diagnosis and therapy of prostate cancer

“…Exosomal miR-34a can be used as a predictive biomarker for the response to docetaxel [ 53 ]. A recent study showed that miR-182 of miR-183 cluster family was detected in prostate cancer cells derived exosomes from the serum [ 61 ].…”

Vesiculated Long Non-Coding RNAs: Offshore Packages Deciphering Trans-Regulation between Cells, Cancer Progression and Resistance to Therapies

“…The protection of nucleic acids in EVs provides a great advantage of storage conditions as well as handling at adverse physical conditions such as fluctuations in temperature and changes in pH, multiple freeze and thaw cycles, and thus could be appealing source for biomarker development [ 1 ]. In particular, the profiling of EV-linked ncRNAs including short ncRNAs such as small nuclear/nucleolar RNAs [ 164 ], miRNAs [ 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 ], as well as lncRNAs from peripheral blood or urine of cancer patients may predict cancer signatures for early diagnosis of specific cancer types [ 75 , 76 , 118 , 165 , 173 , 174 , 175 , 176 ]. Interestingly, the miR-21 one the global tumor marker is found in serum and plasma of various cancer types and may serve as an independent marker of tumor diagnosis [ 95 , 177 , 178 , 179 ].…”