Abstract MicroRNAs (miRNAs) are key players in the integrated regulation of cellular processes, and shape many of the functional properties that define the “cancer stem cell” (CSC) phenotype. Little is known, however, about miRNAs that regulate such properties in human colorectal carcinoma (CRC). In this study, we compared the expression levels of 754 miRNAs between paired samples of EpCAM+/CD44+ cancer cells (enriched in CSCs) and EpCAM+/CD44neg cancer cells (with CSC depletion) sorted in parallel from human primary CRCs, and identified miR-221 as the miRNA that displayed the highest level of preferential expression in EpCAM+/CD44+ cancer cells. High levels of miR-221 expression were associated with Lgr5+ cells in mouse colon crypts and reduced survival in CRC patients. Constitutive over-expression of miR-221 enhanced organoid-forming capacity of both conventional CRC cell lines and patient-derived xenografts (PDXs) in vitro. Importantly, constitutive downregulation of miR-221 suppressed organoid-forming capacity in vitro and substantially reduced the tumorigenic capacity of CSC populations from PDX lines in vivo. […]
miR-221 targets QKI to enhance the tumorigenic capacity of human colorectal cancer stem cells.