<p>Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer</p>

作者：Weihong Ren, XuRan Zhang, Wenbo Li, Qian Feng, Huijie Feng, Yan Tong, Hao Rong, Wei Wang, Dai Zhang, Zhenqiang Zhang, Shichun Tu, Xiaoyan Zhu, Qinxian Zhang · 发表于：Cancer Management and Research · 年份：2019 · DOI：10.2147/cmar.s198886 · 被引用次数：115 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Circular RNAs in diseases

Background: Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the mechanisms of which are largely unknown. Methods: The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and ARG1 , DICER1 , PTEN , PI3K , AKT , mTOR , and NF-kB mRNAs were quantified by quantitative reverse tanscription PCR. Dual-Luciferase Reports Assay were used to examine the expression of genes which was targeted by miR-107. The expression of proteins were analyzed by using western blot. Results: MiR-107 was not only overexpressed in gastric cancer cells but also enriched in their secreted TDEs. Also, these miR-107 enriched TDEs could be taken up by HLA-DR -, CD33 +, MDSCs, where miR-107 was able to target and suppress expression of DICER1 and PTEN genes. Dampened DICER1 expression supported expansion of MDSCs , while decreased PTEN led to activation of the PI3K pathway, resulting in increased ARG1 expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11b +, Gr1 +/high , MDSCs in mouse peripheral blood and altering expression of DICER1 , PTEN , ARG1 , and NOS2 in the MDSCs. Conclusions: Our findings demonstrate for the ...