Abstract
MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) during development and altered expression can cause developmental defects and/or disease. Indeed, aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has been linked to many cancers. Mounting evidence also indicates a role for miRNAs in the development of the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current research on miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentially expressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genes to influence CSC phenotype. Accordingly, we discuss the specific miRNA cluster classifications and isomiRs that are predicted to target the ALDH1, CD166, BMI1, LRIG1, and LGR5 SC genes. miR-23b and miR-92A are of particular interest because our previously reported studies on miRNA expression in isolated normal versus malignant human colonic SCs showed that miR-23b and miR-92a are regulators of the LGR5 and LRIG1 SC genes, respectively. We also identify additional miRNAs whose expression inversely correlated with mRNA levels of their target genes and associated with CRC patient survival. Altogether, our deliberation on miRNAs, their clusters, and isomiRs in regulation of SC genes could provide insight into how dysregulation of miRNAs leads to the emergence of different CSC populations and SC overpopulation in CRC.
Highlights
Our goal is to review current research findings on miRNAs in colorectal cancer (CRC), and to provide an update on miRNAs that target stem cell (SC) genes in CRC
We have reviewed miRNA expression in colon cancer SC (CSC) in order to identify mechanisms that can explain the development of different CSC populations in CRC
Our previous miRNA expression profiling of isolated normal and malignant human colonic SCs showed that miR-23b and miR-92a are regulators of the LGR5 and LRIG1 SC
Summary
Our goal is to review current research findings on miRNAs in colorectal cancer (CRC), and to provide an update on miRNAs that target stem cell (SC) genes in CRC. We will first provide a brief discussion of the discovery of miRNAs and review of the canonical and noncanonical miRNA biogenesis pathways. We will identify how dysregulation of miRNA biogenesis and/or function contributes to cancer. We discuss and identify miRNAs and miRNA clusters that target SC genes or the genes involved in regulating SC properties. We provide bioinformatics information on miRNAs that are predicted to target SC genes in CRC, including their miRNA cluster classification and their isomiRs. The overall focus of this paper is to understand how dysregulation of miRNAs leads to emergence of cancer SC (CSC) populations and SC overpopulation in CRC
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