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Lessons from miR-143/145: the importance of cell-type localization of miRNAs. Nucleic Acids Res 2014 Jul;42(12):7528-38

Date

05/31/2014

Pubmed ID

24875473

Pubmed Central ID

PMC4081080

DOI

10.1093/nar/gku461

Scopus ID

2-s2.0-84903975854 (requires institutional sign-in at Scopus site)   165 Citations

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.

Author List

Kent OA, McCall MN, Cornish TC, Halushka MK

Author

Toby Charles Cornish MD Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Colon
Epithelial Cells
Humans
MicroRNAs
Neoplasms, Glandular and Epithelial