抑制miR-223表达促进巨噬细胞的M2型激活

MiR-223 inhibitor promotes the M2 polarization of macrophage

目的观察microRNA-223(mi R-223)在巨噬细胞M2型激活中的表达及作用。方法运用慢病毒载体感染的方式在巨噬细胞中过表达或敲低miR-223的表达;应用qPCR检测不同激活状态及转染状态巨噬细胞中miR-223的表达;应用Elisa及流式细胞术检测M2型巨噬细胞的激活状态;应用Transwell迁移实验和划痕实验检测乳腺肿瘤细胞的迁移情况。结果 miR-223在单核/巨噬细胞中的表达明显高于肿瘤细胞,在单核细胞向巨噬细胞分化过程中miR-223表达下调,且IL-4或与肿瘤细胞共培养激活的巨噬细胞下调显著。敲低miR-223的表达而不是增加其表达能够促进M2型巨噬细胞标记物CCL18、IL-10和CD206的表达,并促进共培养肿瘤细胞的迁移。结论 miR-223可作为靶向肿瘤微环境调控肿瘤转移的靶点。

Objective To investigate the expression and roles of miR-223 in regulating M2 polarization of macrophage. Methods The expression of miR-223 was detected by using qPCR. The phenotype of miR-223 adjusted macrophage was assayed by flow cytometry and Elisa. The ability of MDAMB-231 cell migration was evaluated by transwell and wound-healing assay. Results MiR-223 was highly expressed in monocytes than in breast cancer cells. The expression of miR-223 was downregulated during monocytes differentiation stimulated by Lipopolysaccharides（LPS）,IL-4 or cocultured with MDAMB-231 cells. And the extent of miR-223 decrease in IL-4 and coculture group was greater than that in LPS treated group. Knockdown of miR-223 level increasesd the expression of M2 type macrophage markers CCL18,IL-10 and CD206,as well as the motility of cocultured MDA-MB-231 cells. Conclusion MiR-223 could serve as a potential target to improve tumor microenvironment and prevent breast tumor metastasis.