掷骰子
转移
癌症研究
巨噬细胞
小RNA
下调和上调
癌细胞
癌症
免疫系统
巨噬细胞极化
生物
细胞生物学
免疫学
RNA干扰
遗传学
核糖核酸
体外
生物化学
基因
作者
Dongping Chen,Juncheng Wang,Zhengyu Liu,P. Li,Ka-Wo Chan,X. Wu,Wudexin Yao,Tingting Yao,Dong-Ming Kuang,Wei Yuan
标识
DOI:10.1016/j.ymthe.2024.02.009
摘要
Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.
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