title: Lessons from miR-143/145: the importance of cell-type localization of miRNAs.
abstract: miR-143 and miR-145 are co-expressed microRNAs (miRNAs) that have been extensively studied as potential tumor suppressors. These miRNAs are highly expressed in the colon and are consistently reported as being downregulated in colorectal and other cancers. Through regulation of multiple targets, they elicit potent effects on cancer cell growth and tumorigenesis. Importantly, a recent discovery demonstrates 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 without consideration that multiple different cell types, each with their own unique miRNA expression patterns, make up each tissue. Herein, we discuss the early reports on the identification of dysregulated miR-143 and miR-145 expression in colorectal cancer and how lack of consideration of cellular composition of normal tissue led to the misconception that these miRNAs are downregulated in cancer. We evaluate mechanistic data from miR-143/145 studies in context of their cell type-restricted expression pattern and the potential of these miRNAs to be considered tumor suppressors. Further, we examine other examples of miRNAs being investigated in inappropriate cell types modulating pathways in a non-biological fashion. Our review highlights the importance of determining the cellular expression pattern of each miRNA, so that downstream studies are conducted in the appropriate cell type.
authors.affiliation: Princess Margaret Cancer Center, University Health Network, 101 College Street, Room 8-703, Toronto Medical Discovery Tower, University of Toronto, Toronto, ON M5G 1L7, Canada.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Kent
authors.affiliation: University of Rochester, Department of Biostatistics, Rochester, NY 14642, USA.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: McCall
authors.affiliation: Johns Hopkins University, Department of Pathology, Baltimore, MD 21205, USA.
authors.forename: Toby C
authors.initials: TC
authors.lastname: Cornish
authors.affiliation: Johns Hopkins University, Department of Pathology, Baltimore, MD 21205, USA mhalush1@jhmi.edu.
authors.forename: Marc K
authors.initials: MK
authors.lastname: Halushka
mesh_terms: D003106:Colon / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000628:therapy
chemical_list: C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs