Molecular pathways: microRNAs, cancer cells, and microenvironment.

One of the most unexpected discoveries in molecular oncology over the last decade is the interplay between abnormalities in protein-coding genes and short noncoding microRNAs (miRNA) that are causally involved in cancer initiation, progression, and dissemination. This phenomenon was initially defined in malignant cells; however, in recent years, more data have accumulated describing the active participation of miRNAs produced by microenvironment cells. As hormones, miRNAs can be released by a donor cell in various forms of vesicles or as "free" molecules secreted by active mechanisms. These miRNAs spread as signaling molecules that are uptaken either as exosomes or as "free" RNAs, by cells located in other parts of the organism. Here, we discuss the communication between cancer cells and the microenvironment through miRNAs. We further expand this in a more translational context and present miRNAs as predictors of treatment response, as crucial agents in targeted therapeutics, and as significant molecules to target. ©2014 American Association for Cancer Research.