Lessons from miR-143/145: the importance of cell-type localization of miRNAs
Open Access
- 28 May 2014
- journal article
- review article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 42 (12), 7528-7538
- https://doi.org/10.1093/nar/gku461
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.Keywords
This publication has 73 references indexed in Scilit:
- MicroRNA-150Circulation: Cardiovascular Genetics, 2013
- Circulating miRNAs as Potential Marker for Pulmonary HypertensionPLOS ONE, 2013
- Treatment of HCV Infection by Targeting MicroRNANew England Journal of Medicine, 2013
- miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasisNature Cell Biology, 2013
- Interaction Domains of Sos1/Grb2 Are Finely Tuned for Cooperative Control of Embryonic Stem Cell FateCell, 2013
- Up-Regulation of microRNA-126 May Contribute to Pathogenesis of Ulcerative Colitis via Regulating NF-kappaB Inhibitor IκBαPLOS ONE, 2012
- MiR-143 is not essential for adipose development as revealed by in vivo antisense targetingBiotechnology Letters, 2012
- RETRACTED ARTICLE: Effect of miR-451 on the Biological Behavior of the Esophageal Carcinoma Cell Line EC9706Digestive Diseases and Sciences, 2012
- RREB1 repressed miR-143/145 modulates KRAS signaling through downregulation of multiple targetsOncogene, 2012
- Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathwayGenes & Development, 2010