The Role of miRNAs, miRNA Clusters, and isomiRs in Development of Cancer Stem Cell Populations in Colorectal Cancer

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.

Establishment and Validation of a Peroxisome-related Gene Signature for Prognostic Prediction and Immune Distinction in Hepatocellular Carcinoma

“…Cancer stem cells (CSCs) have been classified as a small subset of tumor cells with the characteristics to influence self-renewal and differentiation, which makes it hard to eliminate the tumor [54]. CSCs have been identified in numerous solid tumors, such as breast cancer, colon cancer, and HCC [55][56][57]. We further analyzed the relationship of the expression of peroxisome-related genes with RNAss in HCC.…”

Ligands as Stabilizers of G-Quadruplexes in Non-Coding RNAs

“…This study evaluated the formation of G4 in the genomic cluster near three distinct microRNAs, namely, miR-23b, miR-27b, and miR-24 (cluster miR-23b-27b-24-1). The miR clusters can display tumor-suppressive or oncogenic roles depending on their context, as well as the individual members of the cluster that are able to adopt suppressor or oncogenic promoter behaviors according to the cancer type [77]. The authors found three potential G4 sequences capable of folding in antiparallel, and one in parallel, conformations, and tested six small molecules (tetrandrine, fangchinoline, palmatine, jatrorrhizine, berberine and cepharanthine; Scheme 1) [76].…”

“…depending on their context, as well as the individual members of the cluster that are able to adopt suppressor or oncogenic promoter behaviors according to the cancer type [77]. The authors found three potential G4 sequences capable of folding in antiparallel, and one in parallel, conformations, and tested six small molecules (tetrandrine, fangchinoline, palmatine, jatrorrhizine, berberine and cepharanthine; Scheme 1) [76].…”

MicroRNA Methylome Signature and Their Functional Roles in Colorectal Cancer Diagnosis, Prognosis, and Chemoresistance

“…Although the specific mechanism underlying microRNA deregulation in cancer has yet to be determined, multiple studies have demonstrated that epigenetic mechanisms play a significant role in the regulation of microRNA expression in cancer cells [13][14][15], particularly DNA methylation, which is a biological process that adds methyl groups (CH 3 ) to the cytosine ring, thus producing 5-methylcytosine (5mC) (Figure 1a). Expression of microRNAs might be epigenetically regulated via DNA methylation of CpG islands located at promoter regions [13] (Figure 1b,c).…”