Analysis of the exosomal content using miRNA microarray identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via down-regulation of the tumor suppressive nuclear receptor co-repressor NCOR1. These results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC-derived exosomes in the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma.
GA-hMSC–derived exosomes contain a unique miRNA profile.
A and B, miRNA profiles for GA-hMSC and GA-hMSC–derived exosomes, demonstrating a significant (P < 0.001) difference in miRNA content. A, Three hundred and twenty miRNAs were selected by identifying the top 200 miRNAs for each pair of GA-hMSC and GA-hMSC–derived exosomes according to the absolute fold change and collapsing them into nonduplicated miRNAs. B, The top 20 miRNAs and the 8 miRNAs that were highly expressed and highly enriched in exosomes were selected as in A and subjected to cluster analysis. C, Distribution of the average expression level for miRNA in exosomes four GA-HMSC lines, compared with the parental cell. Exosome-enriched miRNAs were both highly expressed (>5,000 hybridization intensity) and highly enriched (>3.0 SD) compared with exosome-depleted miRNA, which were both highly expressed (>5,000 hybridization intensity) and highly enriched (<−1.0 SD) in parental cells. D, Expression levels of predicted gene targets of the exosomal miRNA are significantly (P < 0.01) decreased in GSCs after treatment with GA-hMSC–derived exosomes. Exo, exosome.