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This article has been peer reviewed. It was published in: International Journal of Molecular Sciences.

Volume 22, Issue 3, 1 February 2021, Article number 1424, Pages 1-18.

The published version is available at

Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://


MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) duringdevelopment and altered expression can cause developmental defects and/or disease. Indeed,aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has beenlinked to many cancers. Mounting evidence also indicates a role for miRNAs in the developmentof the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current researchon miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentiallyexpressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genesto influence CSC phenotype. Accordingly, we discuss the specific miRNA cluster classifications andisomiRs that are predicted to target theALDH1,CD166,BMI1,LRIG1, andLGR5SC genes.miR-23bandmiR-92Aare of particular interest because our previously reported studies on miRNA expressionin isolated normal versus malignant human colonic SCs showed thatmiR-23bandmiR-92aareregulators of theLGR5andLRIG1SC genes, respectively. We also identify additional miRNAs whoseexpression inversely correlated with mRNA levels of their target genes and associated with CRCpatient survival. Altogether, our deliberation on miRNAs, their clusters, and isomiRs in regulationof SC genes could provide insight into how dysregulation of miRNAs leads to the emergence ofdifferent CSC populations and SC overpopulation in CRC.

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This work is licensed under a Creative Commons Attribution 4.0 License.

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