Editors' ChoiceMICRORNAs

Sending a Package Through the Blood

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Science Signaling  20 Jul 2010:
Vol. 3, Issue 131, pp. ec220
DOI: 10.1126/scisignal.3131ec220

MicroRNAs (miRNAs), small noncoding RNAs that suppress the translation or promote the degradation of target messenger RNAs, have been identified in serum, where their characteristic patterns of expression in association with various diseases have led to their proposed use as biomarkers. Noting that miRNAs have been found in microvesicles shed from cultured cells, Zhang et al. explored the possibility that microvesicles might enable miRNA transport through serum and its delivery to target cells. Analyses of microvesicles isolated from human plasma or from the medium of the THP-1 human monocyte/macrophage cell line revealed the presence of miRNAs. A comparison of miRNAs in plasma-derived microvesicles to those in microvesicle-free plasma revealed that some miRNAs (including miR-150) were mainly present in microvesicles, whereas others were not. Microvesicles from human blood treated with lipopolysaccharide showed increased miR-150, and other immune-related miRNAs, whereas the abundance of other miRNAs was unchanged. Various stimuli [oleic acid/palmitic acid, advanced glycation end products (AGE), or H2O2] elicited distinct changes in THP-1 miRNA content and that of THP-1–derived microvesicles; all three treatments, however, increased microvesicle miR-150. Fluorescently labeled THP-1–derived microvesicles were internalized by cultured human microvascular endothelial HMEC-1 cells, and HMEC-1 miR-150 content increased after exposure to THP-1–derived microvesicles, whereas that of the miR-150 target c-Myb decreased. THP-1–derived microvesicles stimulated HMEC-1 migration across Transwell filters, an effect that was enhanced with microvesicles from cells treated with AGE but lacking with microvesicles derived from miR-150–deficient THP-1 cells. Intravenous injection of THP-1–derived microvesicles led to an increase in mouse blood vessel miR-150, and microvesicles from the plasma of people with atherosclerosis, which were high in miR-150, decreased HMEC-1 c-Myb and increased HMEC-1 migration. The authors thus conclude that miRNAs may be secreted to act as intercellular signaling molecules that can affect recipient cell function.

Y. Zhang, D. Liu, X. Chen, J. Li, L. Li, Z. Bian, F. Sun, J. Lu, Y. Yin, X. Cai, Q. Sun, K. Wang, Y. Ba, Q. Wang, D. Wang, J. Yang, P. Liu, T. Xu, Q. Yan, J. Zhang, K. Zen, C.-Y. Zhang, Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol. Cell 39, 133–144 (2010). [PubMed]

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