microRNAs in cancer stem cells: Biology, pathways, and therapeutic opportunities

Abstract

Cancer stem cells (CSCs) are a small subpopulation of tumor cells that have been identified in most types of cancer. Features that distinguish them from the bulk of tumor cells include their pluripotency, self‐renewal capacity, low proliferation rate, and tumor‐initiating ability. CSCs are highly malignant, as they confer drug resistance and facilitate tumor progression, relapse, and metastasis. The molecular mechanisms underlying CSC biology are now beginning to be understood. In this context, microRNAs (miRNAs) occupy a prominent place. These endogenous, small noncoding RNA molecules control gene expression at the posttranscriptional level. This study reviews our current understanding of how the misexpression of tumor suppressor and oncogenic miRNAs in CSCs sustain their abundance and malignant properties. We discuss how they partly do so by acting on major CSC signaling pathways, including the Wnt, Notch, Hedgehog, and BMI‐1 pathways. Our current knowledge of miRNA functions in CSCs may now be used for cancer diagnostic and prognostic purposes. In addition, when combined with recent technical advances in the in vivo delivery of miRNAs, we are now in an excellent position to develop strategies that harness miRNA interference and replacement technologies for the therapeutic targeting of CSCs.

Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy

“…Numerous studies have shown that miRNAs are evolutionarily conserved and are key regulators of diverse biological processes such as development, cell proliferation and differentiation, apoptosis and metabolism [61]. MiRNAs also have important regulatory roles in disease progression, including oncogenesis [62, 63]. The molecular mechanisms that control miRNA expression are therefore of critical importance in better understanding normal physiologic processes and disease pathogenesis.…”

“…The molecular mechanisms that control miRNA expression are therefore of critical importance in better understanding normal physiologic processes and disease pathogenesis. Recently, DNA methylation has emerged as a key regulatory mechanism of miRNA expression in several different tissues and disease states [62–65].…”

Cancer Stem Cells Regulation with a Sublingual Nanotherapy using Ultra Low Doses of Non-Coding RNAs

“…Several lines of evidence have shown the critical roles of ncRNAs in CSCs biology [13][14][15][16][17][18][19][20][21][22]. Accumulating evidence has provided insights into the importance of ncRNAs as regulators in several critical steps of cancer development, such as carcinogenesis, cancer invasion, and metastasis.…”

“…Figure 6: miRNAs in regulating cancer stem cells characteristics Key microRNAs have been described to affect the main signaling pathways regulating CSCs. It was for example showed that different microRNAs affect [14]: -Wnt signaling → for instance miR-600 or miR-217 -Notch signaling → miR-34a or miR-141 -Hedgehog signaling → miR-324-5p or miR-326 miRNAs are key intracellular regulators of gene expression and play roles in tumor initiation and distant metastasis via controlling CSCs properties. Some of these miRNAs have tumor suppressor properties, whereas others act as oncogenes [13].…”

MicroRNA Expression Profiling of Normal and Malignant Human Colonic Stem Cells Identifies miRNA92a as a Regulator of the LRIG1 Stem Cell Gene

“…In CRC, differential miRNA expression has been related to stage and site of the tumor [11]. Mounting evidence also indicates a role for miRNAs in the maintenance of the CSC phenotype [12][13][14][15][16]. We have been focusing on miRNAs that contribute to maintenance of the phenotype of colonic CSCs.…”