[Effect of exosome-derived miR-223 from macrophages on the metastasis of gastric cancer cells].

To investigate the effect and mechanism of exosome-derived miR-223 from macrophage on gastric cancer (GC) cell metastasis. Exosomes isolated from macrophages culture medium were characterized and cocultured with GC cell, the miRNA level was detected by qRT-PCR. The migration and invasion of GC cell were detected by transwell. The internalization of exosomes, transfer of miR-223 was observed by immunofluorescence. Macrophage were transfected with a miR-223 inhibitor or negative control, transwell and scratch test were employed to explore the effect of macrophage derived exosome on the migration and invasion of GC cell. Western blot and RT-PCR assay were performed to uncover the underlying mechanisms of miR-223 and PTEN-PI3K/AKT pathway. This study showed that macrophage and macrophage-derived exosomes promoted the migration and invasion of gastric cancer cell(253.2±6.3, 451.8±12.8, 453.4±14.4, all <0.01, and 98.4±5.1, 276.5±10.3, 257.3±8.5, all <0.01, respectively). miR-223 was enriched in macrophage-derived exosomes, which was transferred to the co-cultivated gastric cancer cells. miR-223 knockdown in macrophage reversed the migration and invasion of exosomes on gastric cancer cells(215.6±9.2, 402.5±11.6, 253.7±10.4, all <0.01, and 91.5±8.2,263.4±9.3,105.8±9.3,all <0.01, respectively).Functional studies revealed that exosomal miR-223 derived from macrophage promoted the metastasis of GC cells via the PTEN-PI3K/AKT pathway. In addition, itshowed thatthe actin cytoskeleton was altered, and multiple proteins associated with epithelial-mesenchymaltransition (EMT) were upregulated. Exosomal transfer of macrophage-derived miR-223 promote the metastasis of GC cells through targeting the PTEN-PI3K/AKT pathway.