Study on the effect of miR-223 derived from macrophage exosomes on the metastasis of gastric cancer cells

November 26, 2020  Source: drugdu 271

Henan Provincial People’s Hospital Zheng Peiming, Gao Huijie, Li Junmeng, et al. select macrophages and their exosomes to co-culture with gastric cancer cells (not set as a control group) to detect the expression of miR-223 and observe its influence on the metastatic ability of gastric cancer cells. Fluorescence microscope was used to observe whether macrophages delivered miR-223 to gastric cancer cells through exosomes. Macrophages were transfected with miR-223 antagonist, exosomes were isolated and co-cultured with gastric cancer cells, transwell and scratch experiments were performed to observe their effects on gastric cancer cell metastasis, reverse transcription polymerase chain reaction (RT-PCR), Western blot detection on expression of protein tyrosine phosphatase (PTEN) and of transfer-related proteins.

The results showed that after macrophages and their exosomes were co-cultured with gastric cancer cells, the metastasis and invasion ability of gastric cancer cells was enhanced [253.2±6.3 (control group), 451.8±12.8, 453.4±14.4, all P<0.01 compared with control group ; 98.4±5.1 (control group), 276.5±10.3, 257.3±8.5, all P<0.01 compared with the control group], the difference of relative expression of miR-223 (1.00±0.00, 8.83±0.91, 9.57±1.03) was statistically significant (all P<0.05). Fluorescence microscope observation showed that macrophages delivered miR-223 to gastric cancer cells through exosomes. After blocking the expression of miR-223 in macrophages, the ability of exosomes from which the miR-223 were derived to promote the metastasis and invasion of gastric cancer cells were significantly reduced (215.6±9.2, 402.5±11.6, 253.7±10.4, all P<0.01; 91.5±8.2, 263.4± 9.3, 105.8±9.3, all P<0.01). The expression of PTEN mRNA decreased after gastric cancer cells and macrophage-derived exosomes were co-cultured (1.00±0.00 vs. 0.26±0.03), and the relative expression level was statistically significant (P<0.05); PI3K/AKT pathway was activated, and the cytoskeleton was reconstructed. This activation is weakened when miR-223 metastasis is blocked.

Macrophages deliver miR-223 to gastric cancer cells through exosomes, target PTEN and activate the PI3K/AKT signaling pathway to promote the metastasis of gastric cancer cells. (Bioon.com)

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