Microenvironmental regulation of cancer metastasis by miRNAs

• miRNAs are able to regulate metastasis through modulating tumor microenvironment.
• Mechanistically, miRNAs regulate tumor cell membrane and secreted proteins.
• Mature miRNAs can also be transmitted between tumor cells and stromal cells.
• miRNAs regulating tumor–stroma interactions may serve as new therapeutic targets.

miRNAs are a class of small, non-coding RNAs that regulate cancer progression, especially the processes of invasion and metastasis. Although earlier studies in metastasis primarily focused on the impact that miRNAs have on the intrinsic properties of cancer cells, recent reports reveal that miRNAs also shape interactions between cancer cells and their associated stroma. In this review, we discuss current known mechanisms by which miRNAs execute their microenvironmental regulation of cancer metastasis, including regulating expression of cell membrane-bound and secreted proteins or directly transmitting mature miRNAs between different cell types. The significance of miRNA-mediated tumor–stroma interactions in regulating metastasis suggests that miRNAs may be a potential therapeutic target.