SURVEY AND SUMMARY Lessons from miR-143/145: the importance of cell-type localization of miRNAs

miR-143 and miR-145 are co-expressed microRNAs (miRNAs) that have been extensively studied as po-tential tumor suppressors. These miRNAs are highly expressed in the colon and are consistently reported as being downregulated in colorectal and other can-cers. Through regulation of multiple targets, they elicit potent effects on cancer cell growth and tu-morigenesis. Importantly, a recent discovery demon-strates that miR-143 and miR-145 are not expressed in colonic epithelial cells; rather, these two miRNAs are highly expressed in mesenchymal cells such as fibroblasts and smooth muscle cells. The expression patterns of miR-143 and miR-145 and other miRNAs were initially determined from tissue level data with-out consideration that multiple different cell types, each with their own unique miRNA expression pat-terns, make up each tissue. Herein, we discuss the early reports on the identification of dysregulated miR-143 and miR-145 expression in colorectal can-cer and how lack of consideration of cellular com-position of normal tissue led to the misconception that these miRNAs are downregulated in cancer. We evaluate mechanistic data from miR-143/145 stud-ies in context of their cell type-restricted expres-sion pattern and the potential of these miRNAs to be considered tumor suppressors. Further, we ex-amine other examples of miRNAs being investigated in inappropriate cell types modulating pathways in a non-biological fashion. Our review highlights the im-portance of determining the cellular expression pat-tern of each miRNA, so that downstream studies are conducted in the appropriate cell type