We propose an original strategy for metastasis prevention using a combination of three microRNAs that blocks the dedifferentiation of cancer cells in a metastatic niche owing to the downregulation of stemness genes. Transcriptome microarray analysis was applied to identify the effects of a mixture of microRNAs on the pattern of differentially expressed genes in human breast cancer cell lines. Treatment of differentiated CD44^– cancer cells with the microRNA mixture inhibited their ability to form mammospheres in vitro. The combination of these three microRNAs encapsulated into lipid nanoparticles prevented lung metastasis in a mouse model of spontaneous metastasis. The mixture of three microRNAs (miR-195–5p/miR-520a/miR-630) holds promise for the development of an antimetastatic therapeutic that blocks tumor cell dedifferentiation, which occurs at secondary tumor sites and determines the transition of micrometastases to macrometastases.

中文翻译：

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使用 microRNA 组合抑制干基因来预防转移

我们提出了一种预防转移的原始策略，使用三种 microRNA 的组合，由于干性基因的下调，阻止转移微环境中癌细胞的去分化。应用转录组微阵列分析来鉴定 microRNA 混合物对人乳腺癌细胞系差异表达基因模式的影响。用 microRNA 混合物处理分化的 CD44^癌细胞抑制了它们在体外形成微球的能力。封装在脂质纳米颗粒中的这三种 microRNA 的组合可预防自发转移小鼠模型中的肺转移。三种 microRNA (miR-195–5p/miR-520a/miR-630) 的混合物有望开发出一种抗转移疗法，该疗法可阻止肿瘤细胞去分化，这种去分化发生在继发性肿瘤部位，并决定微转移向大转移的转变。