Abstract：Objective: To explore the effect and mechanism of gastric cancer exosomal lncRNA CASC11 on the polarization of M2 macrophages. Methods: Human monocyte THP-1 was added to PMA to induce differentiation into M0 macrophages, M0 macrophages and gastric cancer cells MGC-803 were transfected with blank plasmids (Vector group) and lncRNA CASC11 overexpression plasmids (lncRNA CASC11) Group). The expression of iNOS, CD16, CD206, Arg-1, Ym1, TNF-α, IL-1β, TGF-β and IL-10 mRNA in macrophages was detected by qRT-PCR. Proportion of CD206+CD14+ cells was detected by flow cytometry. Extract the exosomes secreted by human gastric mucosal cells GES-1, human gastric cancer cell lines MGC-803, SGC7901, MKN45, and MGC803 cells in Vector and lncRNA CASC11 group (GES-1 exo, MGC-803 exo, MKN45 exo, SGC7901 exo, Vector exo, CASC11exo), qRT-PCR was used to detect the expression of lncRNA CASC11 in GES-1, MGC-803, SGC7901, MKN45 cells, transfected MGC-803 cells and their exosomes. M0 macrophages was co-incubated with PBS, GES-1 exo, MGC-803 exo, MKN45 exo, SGC7901 exo, Vector exo, CASC11exo, qRT-PCR was used to detect the expression of lncRNA CASC11, iNOS, CD16, CD206, Arg-1, Ym1, TNF-α, IL-1β, TGF-β and IL-10, and the proportion of CD206+CD14+ cells. Western blot was used to detect the expression of TLR4 and the level of NF-κB phosphorylation. Results: lncRNA CASC11 is highly expressed in gastric cancer cells and their exosomes. Compared with the Vector group, in the lncRNA CASC11 group, the expressions of iNOS, CD16, TNF-α and IL-1β were significantly down-regulated, and the expressions of CD206, Arg-1, Ym1, TGF-β and IL-10 were significantly up-regulated, and the proportion of CD206+ CD14+ cells has increased significantly. Compared with the PBS group, the expressions of iNOS, CD16, TNF-α and IL-1β in macrophages of MGC-803 exo, MKN45 exo and SGC7901 exo groups were significantly down-regulated, lncRNA CASC11, CD206, Arg-1, Ym1, TGF-β and IL-10 expression was significantly up-regulated, the proportion of CD206+ CD14+ cells was significantly increased, and TLR4 expression and NF-κB phosphorylation levels were significantly reduced. Compared with Vector exo, the expression of lncRNA CASC11 in CASC11 exo was significantly increased. Compared with the Vector exo group, the expression of iNOS, CD16, TNF-α and IL-1β in the macrophages of the CASC11 exo group was significantly down-regulated, and the expression of lncRNA CASC11, CD206, Arg-1, Ym1, TGF-β and IL-10 were significantly up-regulated, the proportion of CD206+CD14+ cells was significantly increased, and the expression of TLR4 and NF-κB phosphorylation levels were significantly reduced. Conclusion: Gastric cancer exosomal lncRNA CASC11 inhibits the TLR4/NF-κB signaling pathway and induces polarization of M2 macrophages.
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2021, Vol. 27 
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