MicroRNAs (miRNAs) are a class of noncoding RNAs that regulate target gene expression at the posttranscriptional level. Here, we report that secreted miRNAs can serve as signaling molecules mediating intercellular communication. In human blood cells and cultured THP-1 cells, miR-150 was selectively packaged into microvesicles (MVs) and actively secreted. THP-1-derived MVs can enter and deliver miR-150 into human HMEC-1 cells, and elevated exogenous miR-150 effectively reduced c-Myb expression and enhanced cell migration in HMEC-1 cells. In vivo studies confirmed that intravenous injection of THP-1 MVs significantly increased the level of miR-150 in mouse blood vessels. MVs isolated from the plasma of patients with atherosclerosis contained higher levels of miR-150, and they more effectively promoted HMEC-1 cell migration than MVs from healthy donors. These results demonstrate that cells can secrete miRNAs and deliver them into recipient cells where the exogenous miRNAs can regulate target gene expression and recipient cell function.

BackgroundEndothelial E-selectin has been shown to play a pivotal role in mediating cell–cell interactions between breast cancer cells and endothelial monolayers during tumor cell metastasis. However, the counterreceptor for E-selectin and its role in mediating breast cancer cell transendothelial migration remain unknown.Methodology/Principal FindingsBy assessing migration of various breast cancer cells across TNF-α pre-activated human umbilical vein endothelial cells (HUVECs), we found that breast cancer cells migrated across HUVEC monolayers differentially and that transmigration was E-selectin dependent. Cell surface labeling with the E-selectin extracellular domain/Fc chimera (exE-selectin/Fc) showed that the transmigration capacity of breast cancer cells was correlated to both the expression level and localization pattern of E-selectin binding protein(s) on the tumor cell surface. The exE-selectin/Fc strongly bound to metastatic MDA-MB-231, MDA-MB-435 and MDA-MB-468 cells, but not non-metastatic MCF-7 and T47D cells. Binding of exE-selectin/Fc was abolished by removal of tumor cell surface sialyl lewis x (sLex) moieties. Employing an exE-selectin/Fc affinity column, we further purified the counterreceptor of E-selectin from metastatic breast cancer cells. The N-terminal protein sequence and cDNA sequence identified this E-selectin ligand as a ∼170 kD human CD44 variant 4 (CD44v4). Purified CD44v4 showed a high affinity for E-selectin via sLex moieties and, as expected, MDA-MB-231 cell adhesion to and migration across HUVEC monolayers were significantly reduced by down-regulation of tumor cell CD44v4 via CD44v4-specific siRNA.Conclusions/SignificanceWe demonstrated, for the first time, that breast cancer cell CD44v4 is a major E-selectin ligand in facilitating tumor cell migration across endothelial monolayers. This finding offers new insights into the molecular basis of E-selectin–dependent adhesive interactions that mediate breast cancer cell transendothelial metastasis.

Recent studies show that, at the initial stage of chemical vapor deposition (CVD) of graphene, the isolated carbon monomers will form defective carbon clusters with pentagons that degrade the quality of synthesized graphene. To circumvent this problem, we demonstrate that high-quality centimeter-sized graphene sheets can be synthesized on Cu foils by a selfassembled approach from defect-free polycyclic aromatic hydrocarbons (PAHs) in a high vacuum (HV) chamber without hydrogen. Different molecular motifs, namely coronene, pentacene, and rubrene, can lead to significant difference in the quality of resulting graphene. For coronene, monolayer graphene flakes with an adequate quality can be achieved at a growth temperature as low as 550 °C. For the graphene obtained at 1000 °C, transport measurements performed on back-gated fieldeffect transistors (FETs) with large channel lengths (∼30 μm) exhibit a carrier mobility up to ∼5300 cm 2 V −1 s −1 at room temperature. The underlying growth mechanism, which mainly involves surface-mediated nucleation process of dehydrogenated PAHs rather than segregation or precipitation process of small carbon species decomposed from the precursors, has been systematically investigated through the first-principles calculations. Our findings pave the way for optimizing selection of solid carbon precursors and open up a new route for graphene synthesis.

A novel self-assembled monolayer (SAM) on AlOy /TiOx is terminated with cyclohexyl groups, an unprecedented terminal group for all kinds of SAMs. The SAM-modified AlOy /TiOx functions as a general dielectric, enabling organic thin-film transistors with a field-effect mobility higher than 5 cm(2) V(-1) s(-1) for both holes and electrons, good air stability with low operating voltage, and general applicability to solution-processed and vacuum-deposited n-type and p-type organic semiconductors.

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