Exosomal miR-487a derived from m2 macrophage promotes the progression of gastric cancer

微泡 生物 癌症研究 细胞生长 小RNA 癌症 MTT法 M2巨噬细胞 癌细胞 分子生物学 体外 转移 癌变 巨噬细胞 生物化学 遗传学 基因
作者
Yang Xue-feng,Shuang Cai,Yue Shu,Xun Deng,Yuanwei Zhang,Nian He,Lei Wan,Chen Xu,Yan Qu,Shouyang Yu
出处
期刊:Cell Cycle [Informa]
卷期号:20 (4): 434-444 被引量:32
标识
DOI:10.1080/15384101.2021.1878326
摘要

Tumor-associated macrophages contribute to cell growth, development, and metastasis in various cancers. However, the underlying mechanisms of M2 macrophage that modulate the progression of gastric cancer (GC) remain largely unknown. In this study, we detected the ratio of macrophages in GC tissues and found that the proportion of M2 macrophages was increased in GC tissues. We then co-cultured GC cells with M1 and M2 macrophages, respectively, and then assessed cell proliferation and tumorigenicity of GC cells by MTT and colony formation assay. The results indicated that M2 macrophages promoted the proliferation of GC cells, but M1 not. Besides, GW4869, an exosomes inhibitor, reduced the effects induced by M2 macrophage. Then, we isolated and identified exosomes derived from M1 and M2 macrophage, and confirmed that the exosomes could be taken up by GC cells. We demonstrated that M2 macrophage-exosomes could induce the proliferation and tumorigenesis in vitro and in vivo. Moreover, miR-487a was enriched in M2 macrophage-exosomes and further determined that miR-487a exert the functions by targeting TIA1. In conclusion, exosomal miR-487a derived from M2 macrophage promotes the proliferation and tumorigenesis in gastric cancer, and the novel findings might be helpful to the development of novel diagnostic and therapeutic methods in GC.
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